Chemicals

Conspiracy to Hide Viral Role in Lung Cancer

Anti-smoker propaganda claims that "Scientists may have found a way to tell which smokers are at highest risk of developing lung cancer: measuring a telltale genetic [sic] change inside their windpipes." Dr. Avrum Spira et al. found that some current or former smokers with lung cancer or precancerous lesions had higher activity of a certain enzyme in their upper airways than those who didn't. "[T]he genes involved were part of a well-known cancer-causing pathway named the PI3K pathway. When PI3K-related genes are too active, too much cell growth can occur, but most studies have examined those genes only in tumors." Six of nine patients treated with experimental drugs had there lesions improve. It's dressed up with deceitful rhetoric that "Smoking bathes the entire respiratory tract in toxins." (Developing test to warn smokers of cancer danger. By Lauran Neergaard, AP Medical Writer, Apr. 8, 2010.)

Developing test to warn smokers of cancer danger / Yahoo News

Airway PI3K Pathway Activation Is an Early and Reversible Event in Lung Cancer Development. AM Gustafson, R Soldi, C Anderlind, MB Scholand, J Qian, X Zhang, K Cooper, D Walker, A McWilliams, G Liu, E Szabo, J Brody, PP Massion, ME Lenburg, S Lam, AH Bild, A Spira. Sci Transl Med 2010 Apr 7;2(26):26ra25. "Although only a subset of smokers develop lung cancer, we cannot determine which smokers are at highest risk for cancer development, nor do we know the signaling pathways altered early in the process of tumorigenesis in these individuals. On the basis of the concept that cigarette smoke creates a molecular field of injury throughout the respiratory tract, this study explores oncogenic pathway deregulation in cytologically normal proximal airway epithelial cells of smokers at risk for lung cancer. We observed a significant increase in a genomic signature of phosphatidylinositol 3-kinase (PI3K) pathway activation in the cytologically normal bronchial airway of smokers with lung cancer and smokers with dysplastic lesions, suggesting that PI3K is activated in the proximal airway before tumorigenesis. Further, PI3K activity is decreased in the airway of high-risk smokers who had significant regression of dysplasia after treatment with the chemopreventive agent myo-inositol, and myo-inositol inhibits the PI3K pathway in vitro. These results suggest that deregulation of the PI3K pathway in the bronchial airway epithelium of smokers is an early, measurable, and reversible event in the development of lung cancer and that genomic profiling of these relatively accessible airway cells may enable personalized approaches to chemoprevention and therapy. Our work further suggests that additional lung cancer chemoprevention trials either targeting the PI3K pathway or measuring airway PI3K activation as an intermediate endpoint are warranted."

Gustafson - Sci Transl Med 2010 abstract / PubMed

BUT - What they're testing for, activation of the PI3K system, is actually a sign of virus infection. "A number of viruses including EBV, HPV, HBV and HCV have the ability to establish long-term infections in the host, either through the establishment of latent or chronic infections, which can ultimately lead to cellular transformation. It appears that the gene products of these viruses stimulate PI3K–Akt-mediated cell survival and thereby block apoptosis of the cells they infect. This contributes to both virus survival and oncogenic transformation..." (The pivotal role of phosphatidylinositol 3-kinase–Akt signal transduction in virus survival. S Cooray. J Gen Virol 2004;85:1065-1076.) And among that list of viruses, HPV is implicated in at least a quarter of non-small cell lung cancers. The Surgeon General et al. are guilty of fraud for ignoring the role of HPV in order to falsely blame smoking and passive smoking.

Cooray / J Gen Virol 2004 full article

Human papillomavirus can escape immune recognition through Langerhans cell phosphoinositide 3-kinase activation. SC Fausch, LM Fahey, DM Da Silva, WM Kast. J Immunol 2005 Jun 1;174(11):7172-7178. "Langerhans cells (LC), which are located at the sites of primary infection, do not induce a response implicating the targeting of LC as an immune escape mechanism used by HPV. LC incubated with HPV virus-like particles up-regulate the phosphoinositide 3-kinase (PI3-K) pathway and down-regulate MAPK pathways. With the inhibition of PI3-K and incubation with HPV virus-like particles, LC initiate a potent HPV-specific response."

Fausch / J Immunol 2005 full article

"Smoking-Related" DNA Damage Actually Caused By Infection

The anti-smoker lie: Increased DNA damage in children caused by passive smoking as assessed by comet assay and oxidative stress. A Zalataa, S Yahiab, A El-Bakaryc, HM Elsheikha. Mutat Res 2007 May 18;629(2):140-47. 23 ETS-exposed children and 20 non-exposed. Claims that "A significant increase in mean comet tail length indicating DNA damage was observed in ETS-exposed children (P<0.001) compared to controls. ETS-exposed children had significantly (P<0.001) higher MDA [malondialdehyde] level paralleled with significant (P<0.001) decrease in the level of GSH-Px [glutathione peroxidase] and tocopherol fractions compared with controls." And: "Children exposed to ETS exhibited retarded growth, more chest problems, and gastroenteritis than the control." [Higher exposure to enteric pathogens, some of which cause oxidative stress, is a marker of lower socioeconomic level. Numerous chronic viral infections which are well-known to cause DNA damage are more common and at younger ages among lower socioeconomic groups, such as cytomegalovirus and Epstein-Barr virus. -cast.]

Zalataa - Mutat Res 2007 abstract / PubMed

Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines. S Lassoued, R Ben Ameur, W Ayadi, B Gargouri, R Ben Mansour, H Attia. Mol Cell Biochem 2008 Jun;313(1-2):179-186. "The incubation of the different target cells with EBV induced an oxidative stress in the purified B lymphocytes, DG75, and 293, but not in HepG2 and K562. This oxidative stress was highlighted by an increase in MDA level (P < 0.05), which began 2 h after the addition of the virus and persisted after 12 and 24 h. Simultaneously, a decrease in catalase and superoxide dismutase activities was observed (P < 0.05), suggesting an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species (ROS). The efficiency of EBV infection, assessed by viral DNA PCR amplification, was confirmed in 293 and DG75 but not in HepG2, which was in total concordance with their oxidative profiles. In conclusion, the EBV infection of B and epithelial cells leads to the establishment of an oxidative stress which can play a key role during the viral transformation."

Lassoued - Mol Cell Biochem 2008 abstract / PubMed

Study of oxidative-stress in rotavirus infected infant mice. CP Sodhi, R Katyal, SV Rana, S Attri, V Singh. Indian J Med Res 1996 Oct;104:245-249. "Glutathione and related thiols were significantly declined in rotavirus infected group. Superoxide dismutase, glutathione peroxidase and glutathione-S-transferase (1-chloro 2, 4 dinitrobenzene) activities were also decreased in the rotavirus infected group. The activities of glutathione reductase and glutathione-S-transferase (ethacrynic acid) however were elevated with rotavirus infection in comparison to the control group. Similarly, ADP-FeCI3, NADPH induced lipid peroxidation was elevated with rotavirus infection. Thus the altered oxidative/antioxidative profile indicated the presence of oxidative stress in the rotavirus infected group and can be postulated to have a prominent role in the pathogenesis of the disease." (Which shows that even viruses that don't cause cancer can cause oxidative stress - cast)

Sodhi - Indian J Med Res 1996 abstract / PubMed

Sister chromatid exchanges

The anti-smoker lie: No influence of beta-carotene on smoking-induced dna damage as reflected by sister chromatid exchanges. G van Poppel, FJ Kok, P Duijzings, N de Vogel. Int J Cancer 1992 May 28;51(3):355-358. Sister chromatid exchanges (SCE) in lymphocytes in 143 heavy smokers.

van Poppel - Int J Cancer 1992 abstract / PubMed

Sister chromatid exchange and nasopharyngeal carcinoma. GY Li, KT Yao, R Glaser. Int J Cancer 1989 Apr 15;43(4):613-618. "[W]e found that: (1) the spontaneous SCEs in peripheral blood lymphocytes (PBLs) from 75 NPC patients were significantly higher than those of PBLs from 44 normal adults, 24 cord blood (CBL) specimens, and PBLs from 20 patients with chronic inflammation of the nasopharynx; (2) PBLs from NPC patients who were positive for EBV virus capsid antigen (VCA) IgA antibody had a higher SCE frequency as compared with PBLs from VCA IgA-negative NPC patients; (3) the chemical carcinogens used induced significantly higher SCEs in lymphocytes from NPC patients than in PBLs from normal adults and CBLs; (4) the mean SCEs of EBV growth-transformed CBLs increased from 5.17 to 14.12 after infection and was similar to the level of SCEs found in PBLs from the VCA IgA-positive NPC patients." [Epstein-Barr virus is the known cause of nasopharyngeal cancer. -cast]

Li - Int J Cancer 1989 abstract / PubMed

Chemicals vs HPV in bladder cancer: Papillomaviruses underlie supposed chemical carcinogenesis

With state-of-the-art techniques, human papillomaviruses are now found in virtually 100% of cervical cancers. NIH Consensus Statement 102 and the International Agency for Research on Cancer have both declared that HPV causes human cervical cancer. Although they would not admit this, the alleged risk from smoking (and passive smoking) was generated by residual confounding, due to the high odds ratio associated with HPV infection.

The role of human papillomaviruses in bladder cancer has been less well studied. However, there have been more than 27 clinical/laboratory studies, which have indicated a prevalence of high-risk HPV types varying from 2.5% to 81%. HPV-16, which causes most cervical cancer, was the most commonly found type. "In addition, molecular studies suggest that the HPV-related oncoproteins E6 and E7 play a role in bladder carcinogenesis via inactivation and/or degradation of p53 adn pRb suppressor gene-associated proteins" (A Lopez-Beltran, AL Escudero. Human papillomavirus and bladder cancer. Biomed & Pharmacother 1997;51(6-7):252-257).

Chemical carcinogens, both from environmental sources and from smoking, have been alleged to cause bladder cancer. Dietary bracken fern in cattle has been a classic real-life example in animals. There are high rates of both bladder and alimentary tract cancers among cattle which graze on bracken-infested land. Chemical carcinogenesis by substances in the bracken ferns has traditionally gotten the blame. However, there is evidence implicating a role for bovine papilloma viruses, brought on by immunosuppression caused by the toxicity of the bracken fern.

From: Cooperation between bovine papillomaviruses and dietary carcinogens in cancers of cattle. ME Jackson, MS Campo. In: DNA tumor viruses. Oncogenic mechanisms. G Barbanti-Brodano, M Bendinelli, H Friedman, eds. Plenum Press, 1995, Ch 7, pp 111-122.

"However, cattle that were fed bracken but not injected with BPV2 also developed urinary bladder cancers. Nevertheless, BPV2 was found in the bladder cancers from both groups (WFH Jarrett and MS Campo, unpublished data), strongly suggesting that latent asymptomatic virus had been activated by the bracken diet (MS Campo et al. Latent papillomavirus infection in cattle. Res Vet Sci 1994;56:151-157), possibly as a result of the chronic immunosuppression caused by bracken feeding (Evans WC et al. Acute bracken poisoning in homogastric and ruminant animals. Proc Royal Soc Edin 1982;81:29-64). This result was confirmed in an experiment designed to test for synergism between BPV4 and bracken in alimentary tract cancer (see below), in which none of the cattle were experimentally exposed to BPV2, but bladder cancers occurred only in bracken-fed animals, and in 60% of the animals these cancers were positive for BPV2 DNA (MS Campo, WFH Jarrett. CIBA Found Symp 1986;120:117-130; MS Campo, WFH Jarrett. Cancer Res 1992;52:6898-6904). Of the naturally occurring bladder cancers, 46% were also found to be positive for BPV2 DNA. A group of cattle that were kept on a hay diet but immunosuppressed with azathioprine developed BPV2-positive hemangiomas of the bladder, again suggesting that immunosuppression leads to activation of latent virus."

Animal models of papillomavirus carcinogenesis. MS Campo. Virus Res 2002 Nov;89(2)249-261. "Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognized as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans.'"

Campo - Virus Res 2002 abstract / PubMed

It has been claimed that smoking causes immunosuppression, which leads to HPV activation ultimately resulting in cervical cancer. However, the similar supposed risk of cervical cancer trumpeted for passive smokers as for active smokers militates against this. It is not biologically plausible that the effect of a small amount of secondhand smoke is so similar to that of a large amount of firsthand plus secondhand smoke. That active and passive smokers have similar rates of exposure to high-risk HPVs due to lifestyle is the only plausible explanation.

Smokers are said to have higher rates of bacterial vaginosis than nonsmokers, and this has been claimed to be evidence of immunosuppression. However, it is now known that bacterial vaginosis is caused by a virus that infects the normal bacteria of the vagina, and the human host's immune system is not involved. The differences, again, are due to differences in exposure due to lifestyle.

See also:

HPV is implicated in bladder cancer
HPV Strains and Oncogenicity

Bruce Ames and the Bracken Fern

"If you mention the manifesto that started the environmental movement to Bruce Ames [Rachel Carson's book, Silent Spring], he cannot help pointing out a little problem with the opening fable. There was a blight on this town that even its author, Rachel Carson, didn't know about. 'Here's this nice sylvan view of ferns,' Ames says, 'and one of the most common ones, the bracken fern, is absolutely full of carcinogens.' In fact these chemicals, which can be passed on through cow's milk or enter the soil when the plants die, might even be deadlier than the DDT that so concerned Carson, Ames says." (Not to Worry: Bruce Ames Helped Launch the Cancer Scare of the 1960s and 1970s. Now He Says Mushrooms Are More Threatening Than PCBs. Hippocrates 1988 Jan-Feb, p 28). But this view is baloney as well - IT WAS REALLY THE PAPILLOMA VIRUSES THAT CAUSED THE CANCER.

Ames - Hippocrates 1988 / UCSF (pdf, 12 pp)

Bruce Ames and Lois Gold continue to promote junk science

Ames and Gold pretend, among other things, that diet and stomach cancer studies which ignore the existence of Helicobacter pylori supposedly "prove" that fruits and vegetables will prevent stomach cancer -- ignoring the fact that rates of stomach cancer depend most on HP infection, not on how many magic fruits and vegetables people eat; and that the purported "protective" effects of fruits and vegetables is the product of confounding. Ames and Gold are pseudo-debunkers who please the pro-industrialists, while protecting the health fascists' core fraud of ignoring the role of infection. (Politicizing Science: The Alchemy of Policy-Making. By Bruce Ames and Lois Swirsky Gold. Michael Gough, editor. Hoover Institute Press, 2003.)

Ames & Gold, 2003 / Spiked-Online 2004

More Ames & Gold Articles

Be Most Wary of Nature's Own Pesticides. By Bruce N. Ames. Los Angeles Times, Feb. 27, 1989.

Ames, Los Angeles Times 1989 / UCSF (pdf, 1 p)

Too Many Rodent Carcinogens - Mitogenesis Increases Mutagenesis. B.N. Ames, L.S. Gold. Science 1990 Aug 31;249(4972):970-971. (Pages 697-698.)

Ames & Gold, Science 1991 / UCSF (pdf, 709 pp)

Mutagenesis tests

Predicting Rodent Carcinogenicity From Mutagenic Potency Measured in the Ames Salmonella Assay. Bethel A. Fetterman, Byung Soo Kim, Barry H. Margolin, Jonathan S. Schildcrout, Melissa G. Smith, S. Michelle Wagner, Errol Zeigera. Environmental and Molecular Mutagenesis 1997;29:312- 322. "The somatic mutation theory of carcinogenesis holds that mutations are a common first step in the development of a cancer cell; consequently, interest in these STI's has been fueled by their ability to identify potential carcinogens. The test receiving by far the most use and attention has been the Salmonella (SAL) mutagenesis test developed by Ames and colleagues [1973, 1975]. The SAL test gets its most extensive use as a preliminary screen during chemical and drug development. The results of this test are often the only toxicology-related information used by industry to decide whether to proceed with development of the chemical and to more definitive toxicological tests, or to label it a potential carcinogen, and put it aside, with no further testing... Our study firmly establishes that the predictive relationship between quantitative SAL mutagenicity and carcinogenicity is, at best, weak, regardless of the potency measure used. The lack of a strong predictive relationship between SAL mutagenicity and rodent carcinogenicity hardly seems surprising. Mutagenesis may be only the first step in some pathways that lead to cancer. The inference drawn here, however, is that this DNA damage as measured by mutations in SAL is not the rate-limiting consideration in the ultimate development of cancer in rodents. (Funded by the National Institute of Environmental Health Sciences.)

Fetterman - Environmental and Molecular Mutagenesis 1997 full article / UCSF (pdf, 11 pp)

Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens I. Sensitivity, specificity and relative predictivity. D Kirkland, M Aardema, L Henderson, L Müller. Mutat Res 2005 Jul 4;584(1-2):1-256. "The performance of a battery of three of the most commonly used in vitro genotoxicity tests--Ames+mouse lymphoma assay (MLA)+in vitro micronucleus (MN) or chromosomal aberrations (CA) test--has been evaluated for its ability to discriminate rodent carcinogens and non-carcinogens, from a large database of over 700 chemicals compiled from the CPDB ("Gold"), NTP, IARC and other publications... Of the 553 carcinogens for which there were valid genotoxicity data, 93% of the rodent carcinogens evaluated in at least one assay gave positive results in at least one of the three tests... Only 19 carcinogens (out of 206 tested in all three tests, considering CA and MN as alternatives) gave consistently negative results in a full three-test battery. Most were either carcinogenic via a non-genotoxic mechanism (liver enzyme inducers, peroxisome proliferators, hormonal carcinogens) considered not necessarily relevant for humans, or were extremely weak (presumed) genotoxic carcinogens (e.g. N-nitrosodiphenylamine)... " Of 183 chemicals that were non-carcinogenic after testing in both male and female rats and mice, "When all three tests were performed, 75-95% of non-carcinogens gave positive (i.e. false positive) results in at least one test in the battery... The extremely low specificity highlights the importance of understanding the mechanism by which genotoxicity may be induced (whether it is relevant for the whole animal or human) and using weight of evidence approaches to assess the carcinogenic risk from a positive genotoxicity signal. It also highlights deficiencies in the current prediction from and understanding of such in vitro results for the in vivo situation. It may even signal the need for either a reassessment of the conditions and criteria for positive results..."

Kirkland - Mutat Res 2005 abstract / PubMed

Aneuploidy and cancer: from correlation to causation. P Duesberg, R Li, A Fabarius, R Hehlmann. Contrib Microbiol 2006;13:16-44. "Conventional genetic theories have failed to explain why cancer (1) is not found in newborns and thus not heritable; (2) develops only years to decades after 'initiation' by carcinogens; (3) is caused by non-mutagenic carcinogens; (4) is chromosomally and phenotypically 'unstable'; (5) carries cancer-specific aneuploidies; (6) evolves polygenic phenotypes; (7) nonselective phenotypes such as multidrug resistance, metastasis or affinity for non-native sites and 'immortality' that is not necessary for tumorigenesis; (8) contains no carcinogenic mutations. We propose instead that cancer is a chromosomal disease: Accordingly, carcinogens initiate chromosomal evolutions via unspecific aneuploidies. By unbalancing thousands of genes aneuploidy corrupts teams of proteins that segregate, synthesize and repair chromosomes. Aneuploidy is thus a steady source of karyotypic-phenotypic variations from which, in classical Darwinian terms, selection of cancer-specific aneuploidies encourages the evolution and subsequent malignant 'progressions' of cancer cells. The rates of these variations are proportional to the degrees of aneuploidy, and can exceed conventional mutation by 4-7 orders of magnitude. This makes cancer cells new cell 'species' with distinct, but unstable karyotypes, rather than mutant cells. The cancer-specific aneuploidies generate complex, malignant phenotypes, through the abnormal dosages of the thousands of genes, just as trisomy 21 generates Down syndrome. Thus cancer is a chromosomal rather than a genetic disease. The chromosomal theory explains (1) nonheritability of cancer, because aneuploidy is not heritable; (2) long 'neoplastic latencies' by the low probability of evolving competitive new species; (3) nonselective phenotypes via genes hitchhiking on selective chromosomes, and (4) 'immortality', because chromosomal variations neutralize negative mutations and adapt to inhibitory conditions much faster than conventional mutation."

Duesberg - Contrib Microbiol 2006 abstract / PubMed

Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. AJ Sigurdson, IM Jones, Q Wei, X Wu, MR Spitz, DA Stram, MD Gross, WY Huang, LE Wang, J Gu, CB Thomas, DJ Reding, RB Hayes, NE Caporaso. Carcinogenesis 2011 Jan;32(1):69-73. In Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples of 117 lung cancer patients with 117 matched controls, the alkaline Comet assay and the host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide were unrelated to lung cancer risk. In the bleomycin mutagen sensitivity assay, "statistically significantly increased lung cancer odds ratios (OR(adjusted)) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, P(trend) = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (P(trend) = 0.02), supporting the notion the assay may be a measure of cancer susceptibility." [However, infections by both Epstein-Barr virus and cytomegalovirus make cells more susceptible to damage by bleomycin - cast]

Sigurdson - Carcinogenesis 2011 full article / PubMed Central
Sigurdson - Carcinogenesis 2011 full article

And they note that "Our study is the first to prospectively evaluate three widely used mutagen sensitivity assays in relation to lung cancer risk." So, the purveyors of mutagen assays are crassly deceiving the public when they pretend that those assays are relevant.

EBV and CMV Increase Damage From Bleomycin

Chromosome breakage induced by bleomycin in an ataxia telangiectasia lymphoblastoid line: correlation with fragile sites and Epstein-Barr virus DNA localization. D Caporossi, B Tedeschi, P Vernole, B Porfirio, B Nicoletti. Cytogenet Cell Genet 1989;52(3-4):180-185. "[T]he major feature of this subline, ATL9/g, is a stable achromatic gap at 1p32 in one of the chromosomes 1, overlapping a preferential site of EBV localization. The results of this paper show that this gap is highly sensitive to bleomycin-induced damage."

Caporossi - Cytogenet Cell Genet 1989 abstract / PubMed

Cytomegalovirus-enhanced induction of chromosome aberrations in human peripheral blood lymphocytes treated with potent genotoxic agents. CZ Deng, S AbuBakar, MP Fons, I Boldogh, J Hokanson, WW Au, T Albrecht. Environ Mol Mutagen 1992;19(4):304-310. More chromosome aberrations were found in CMV-infected cells treated with bleomycin or hydroxyaminoquinoline-1-oxide, but not with 4-nitroquinoline-1-oxide.

Deng - Environ Mol Mutagen 1992 abstract / PubMed

Differential mutagen sensitivity of peripheral blood lymphocytes from smokers and nonsmokers: effect of human cytomegalovirus infection. T Albrecht, CZ Deng, SZ Abdel-Rahman, M Fons, P Cinciripini, RA El-Zein. Environ Mol Mutagen 2004;43(3):169-178. 20 smokers matched with 20 nonsmokers. "The baseline (background) CA frequency was similar in both smokers and nonsmokers. Significantly higher frequencies of aberrant cells (P < 0.05) were observed in PBLs from smokers compared to nonsmokers at all bleomycin concentrations tested (10, 30 and 100 microg/ml). Infection of PBLs with HCMV induced a significant (P < 0.05) twofold increase in the frequency of CA (primarily chromatid breaks) in PBLs, regardless of the smoking status. PBLs from smokers and nonsmokers infected with HCMV prior to challenge with bleomycin demonstrated significant (P < 0.05) concentration-dependent increases in the levels of aberrant cells chromatid-type damage (breaks), and chromosome-type aberrations (deletions, rearrangements) compared to noninfected cells challenged with bleomycin. The frequency of induced CA was consistently higher for PBLs derived from smokers relative to nonsmokers (P = 0.06 and 0.002)."

Albrecht - Environ Mol Mutagen 2004 abstract / PubMed

Epstein-Barr virus latent membrane protein 1 induces micronucleus formation, represses DNA repair and enhances sensitivity to DNA-damaging agents in human epithelial cells. MT Liu, YR Chen, SC Chen, CY Hu, CS Lin, YT Chang, WB Wang, JY Chen. Oncogene 2004 Apr 1;23(14):2531-2539. "In this study, H1299 cells harboring LMP1 were shown to be more sensitive to UV and bleomycin than those with a vector control. Using various deletion mutants of EBV LMP1 to determine the regions of LMP1 required to enhance MN formation, inhibit DNA repair and sensitize cells to DNA-damaging agents, we found that the region a. a. 189-222 (located within the CTAR1 domain) was responsible for sensitizing cells to UV and bleomycin, as well as for enhancing MN formation and repressing DNA repair."

Liu - Oncogene 2004 abstract / PubMed

Also:

Oral exposure to benzo[a]pyrene in the mouse: detoxication by inducible cytochrome P450 is more important than metabolic activation. S Uno, TP Dalton, S Derkenne, CP Curran, ML Miller, HG Shertzer, DW Nebert. Mol Pharmacol 2004 May;65(5):1225-1237. "The cytochrome P450 (CYP1A1) enzyme metabolically activates many polycyclic aromatic hydrocarbons, including benzo[a]pyrene (BaP), to DNA- and protein-binding intermediates that are associated with toxicity, mutagenesis, and carcinogenesis. As a result, it is widely accepted that CYP1A1 potentiates the toxicity of this class of chemicals. In distinct contrast, we show here that CYP1A1 inducibility is essential in the detoxication of oral BaP. We compared Cyp1a1(-/-) knockout mice, having the genetic absence of the CYP1A1 enzyme, with Cyp1a1(+/+) wild-type mice. At an oral BaP dose of 125 mg/kg/day, Cyp1a1(-/-) mice died within 30 days whereas Cyp1a1(+/+) mice displayed no outward signs of toxicity. The rate of BaP clearance was 4-fold slower in Cyp1a1(-/-) than Cyp1a1(+/+) mice. The cause of death in Cyp1a1(-/-) mice receiving oral BaP seemed to be immunotoxicity, including toxic chemical depression of the bone marrow; some toxic effects in Cyp1a1(-/-) mice were noted at a BaP dose as low as 1.25 mg/kg/day. DNA post-labeling studies demonstrated dramatically higher BaP-DNA adduct levels in all Cyp1a1(-/-) tissues assayed, with the exception of the small intestine, which is probably a major site of BaP metabolism in Cyp1a1(+/+) mice."

Uno - Mol Pharmacol 2004 abstract / PubMed

Unexpected DNA damage caused by polycyclic aromatic hydrocarbons under standard laboratory conditions. KL Platt, S Aderhold, K Kulpe, M Fickler. Mutat Res 2008 Feb 29;650(2):96-103. In V79 lung fibroblasts of the Chinese hamster, which lack enzymes necessary to convert PAHs to DNA-binding metabolites, 11 PAHs including benzo[a]pyrene caused DNA strand breaks even without external metabolic activation, due to photoactivation by white fluorescent laboratory lights. This did not occur in the dark or under yellow fluorescent lights. And: "The genotoxicity of BaP that is metabolically activated in V79 cells stably expressing human cytochrome P450-dependent monooxygenase (CYP1A1) as well as human epoxide hydrolase (V79-hCYP1A1-mEH) could not be detected with the comet assay performed under yellow light. Likewise the DNA-damaging effect of r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BaPDE) observed with the comet assay was only weak. However, upon inhibition of nucleotide excision repair (NER), which is responsible for the removal of stable DNA adducts caused by anti-BaPDE, the tail moment rose 3.4-fold in the case of BaP and 12.9-fold in the case of anti-BaPDE. These results indicate that the genotoxicity of BaP and probably of other compounds producing stable DNA adducts are reliably detected with the comet assay only when NER is inhibited."

Platt - Mutat Res 2008 abstract / PubMed

"Mechanisms of tobacco carcinogenesis" ?????

The Centers for Disease Control

Polycyclic Aromatic Hydrocarbons (PAHs) How Do PAHs Induce Pathogenic Changes? Environmental Health and Medicine Education, Agency for Toxic Substances & Disease Registry, Centers for Disease Control, Jul. 1, 2009. "Benzo(a)pyrene diol epoxide adducts bind covalently to several guanine positions of the bronchial epithelial cell DNA p53 gene, where cancer mutations are known to occur from exposure to cigarette smoke. This is one possible genotoxic mechanism of cancer causation by tobacco [Denissenko 1996]."

Polycyclic Aromatic Hydrocarbons (PAHs) / CDC

But, metastasis of cancer cells without mutated p53 shows that this mutation is not necessary for carcinogenesis and may be a late event.

The Lie That p53 Mutations Are the Mechanism Behind Lung Cancer

The Surgeon blames smoking for methylation of P16 caused by human papillomaviruses, Epstein-Barr virus, hepatitis viruses, and even Helicobacter pylori - all of which are known human carcinogens.

The Surgeon General Lies About Cancer

UK Committees on Toxicity, Carcinogenicity, Mutagenicity of Chemicals in Food, Consumer Products and the Environment

Committees on Toxicity, Carcinogenicity, Mutagenicity of Chemicals in Food, Consumer Products and the Environment, Joint Statement on the Re-Assessment of the Toxicological Testing of Tobacco Products, Nov. 2004:

"2. The Committees (COT/COC/COM) were asked to provide advice on these areas of toxicological assessment with reference to the assessment of Potentially Reduced Exposure Products (PREPS) and in particular tobacco-based PREPS which are smoked. A brief overview of the information reviewed and approach taken by the Committee’s is given below...

"5. The Committees commented that tobacco smoke was a highly complex chemical mixture and that the causative agents for smoke induced diseases (such as cardiovascular disease, cancer, effects on reproduction and on offspring) was unknown. The mechanisms by which tobacco induced adverse effects were not established. The best information related to tobacco smoke - induced lung cancer, but even in this instance a detailed mechanism was not available. The Committees therefore agreed that on the basis of current knowledge it would be very difficult to identify a toxicological testing strategy or a biomonitoring approach for use in volunteer studies with smokers where the end-points determined or biomarkers measured were predictive of the overall burden of tobacco-induced adverse disease...

"12. The COC commented on the complexity of tobacco indiced cancer and noted that the mechanism(s) and information on the chemical agents responsible for tobacco induced cancer in humans had not been fully elucidated. In addition members noted the importance of the interaction between chemical carcinogens and susceptibility factors regarding the pathogenesis of tobacco induced cancer. The COC concluded that there is no strategy which could be used to compare PREPS for carcinogenic potency and that the approaches used are not informative on the risk of tobacco induced carcinogenicity. The COC agreed that it was not possible to draw conclusions on the carcinogenic risk of tobacco-based PREPS on the available biomarker studies reviewed...

Committees on Toxicity, etc. 2004 / Archive.org (pdf, 5 pp)

Update - 2009 Annual Report, UK Committee on Carcinogenicity of Chemicals in Food, Consumer
Products and the Environment

"3.8 The Committee considered that the available studies used to assess the contribution of individual or mixed ingredients or additives to the overall toxicity of tobacco products are inadequate to assess the risks posed by conventional cigarettes, so it is not possible to assess the modulation of that risk resulting from inclusion of additives. The relationship between effect (an increase in biomarker) and exposure is also poorly understood.

"3.9 The Committee considered that the development of biomarkers of harm for tobacco products, particularly in relation to cancer, was a laudable but an unrealistic goal. The carcinogenic mechanisms underlying tobacco carcinogenesis are very complex, and are likely to be different in the various target organs and tissues, so it will be very difficult to identify a suitable comprehensive biomarker of effect. The „omics technologies might provide some alternatives but these would tend to be biomarkers of exposure, rather than effect. Metabonomics might be able to identify biomarkers of early effects in adequately designed prospective studies amongst smokers, although the Committee was sceptical about the likelihood of finding a suitable biomarker.

Committee on Carcinogenicity, 2009 / gov.uk (pdf, 17 pp)

FANCD2

The anti-smoker lie: Cigarette smoke induces genetic instability in airway epithelial cells by suppressing FANCD2 expression. LE Hays, DM Zodrow, JE Yates, ME Deffebach, DB Jacoby, SB Olson, JF Pankow, GC Bagby. Br J Cancer 2008 May 20;98(10):1653-1661. "Here, we show that cigarette smoke condensate (CSC) inhibited translation of FANCD2 mRNA (but not FANCC or FANCG) in normal airway epithelial cells and that this suppression of FANCD2 expression was sufficient to induce both genetic instability and programmed cell death in the exposed cell population. Cigarette smoke condensate also suppressed FANCD2 function and induced CIN in bronchogenic carcinoma cells, but these cells were resistant to CSC-induced apoptosis relative to normal airway epithelial cells. We, therefore, suggest that CSC exerts pressure on airway epithelial cells that results in selection and emergence of genetically unstable somatic mutant clones that may have lost the capacity to effectively execute an apoptotic programme. Carcinogen-mediated suppression of FANCD2 gene expression provides a plausible molecular mechanism for CIN inbronchogenic carcinogenesis."

Hays - Br J Cancer 2008 abstract / PubMed

FANCD2 expression in advanced non-small-cell lung cancer and response to platinum-based chemotherapy. M Ferrer, SW Span, B Vischioni, JJ Oudejans, PJ van Diest, JP de Winter, C Giaccone, FA Kruyt. Clin Lung Cancer 2005 Jan;6(4):250-254. 47 patients. "FANCD2 expression could be detected in 32% of the cases (15 of 47). Expression of FANCD2 was not correlated with any patient or tumor characteristics, and FANCD2 expression was not a predictor of response to chemotherapy or patient survival. In conclusion, the activation status of the FA pathway had no value in predicting sensitivity to platinum-based chemotherapy in patients withadvanced NSCLC."

Ferrer - Clin Lung Cancer 2005 abstract / PubMed

Environmental Benzo[a]pyrene

Choking on a Gnat While Swallowing a Camel

A typical ignorant attitude which is encourage by the health establishment because it furthers their health fascist political agenda (as well as enabling insider trading networks to exploit the effects of public hysteria on stock prices): "If large doses of carcinogens will eventually lead to cancer, why would we want to unnecessarily add to the levels of carcinogens we are exposed to? Thus, why use large amounts of pesticides when less or none will work just fine? Why expose ourselves to the carcinogens found in air pollution, car exhaust, cigarette smoke, etc. if we don't have to? If the dose is the poison, and I'm already getting dosed without trying to, why should I increase my risk?"

For benzo[a]pyrene, which is one of the common polycyclic hydrocarbons produced by combustion, "[T]he food chain is the dominant pathway of human exposure, accounting for about 97% of the total daily intake of BaP. Inhalation and consumption of contaminated water are only minor pathways of human exposure [2% from air, and 1% from water]. The long-term average daily intake of BaP by the general population is estimated to be 2.2 micrograms (µg) per day. Cigarette smoking and indoor activities do not substantially increase human exposure to BaP relative to background levels of BaP present in the environment." And, "[A]verage smokers (i.e., individuals who smoke 20 cigarettes a day) are taking in an additional 780 ng of BaP daily, which means that smokers get an additional 16% BaP from smoking" [based on pre-1979 cigarettes, which contained about twice the quantity of BaP as newer low-tar cigarettes]. Also, the exposure from cooked beef (0.2 -24.1 µg/kg) is less than the exposure from leafy vegetables (7.0 - 48 µg/kg). And, this research was sponsored by the U.S. Environmental Protection Agency. (Benzo-a-pyrene: Environmental partitioning and human exposure. H.A. Hattemer-Frey, C.C. Travis. Toxicology and Industrial Health 1991;7(3):141-157.)

Hattemer-Frey & Travis, Toxicology and Industrial Health 1991 / UCSF (pdf, 17 pp)

Smoke from cigarettes accounts for less than 0.007% of U.S. Bap emissions per year. (Submission by Philip Morris U.S.A. to The National Toxicology Program. Appendix 7, "Benzo[a]pyrene: Environmental Distribution and Human Exposure." March 20, 1998.

Philip Morris to NTP, 1998 / UCSF (pdf, 21 pp)

Risk Assessment of Chemical Carcinogens: Is It Time For A Change? By Robert J. Scheuplein, Director, Office of Toxicological Sciences, Center for Food Safety and Applied Nutrition, Food and Drug Administration. Presented at the Brookings Institution, June 17, 1991. "[D]espite well over 500 papers on cancer risk assessment, on the biassay, on cancer thresholds and numerous related subjects, since 1961 (the date of Mantel and Bryan's paper) -- cancer risk assessment is still more of a regulatory tool than a scientific discipline and rests more on regulatory need than scientific plausibility" "So far, for any carcinogenic or mutagenic response in any given situation, be it man, mouse, isolated organ or a Salmonella plate assay, there is a demonstrable threshold or 'no effect level.' In thousands of studies with hundreds of thousands of animals, not a single carcinogen has been found that has not demonstrated an experimental threshold."

Scheuplein, 1991 / UCSF (pdf, 43 pp)

Determination of polycyclic aromatic hydrocarbons in the lung. H Seto, T Ohkubo, T Kanoh, M Koike, K Nakamura, Y Kawahara. Arch Environ Contam Toxicol 1993 May;24(4):498-503. "Polycyclic aromatic hydrocarbons (PAHs) accumulated in human lung samples from men (n = 236) and women (n = 128) were determined by high-performance liquid chromatography (HPLC) to examine their association with lung cancer. The mean values for benzo[a]pyrene (BaP), benzo[k]fluoranthene (BkF), and benzo[g,h,i]perylene (BghiP) in lungs (ng/g dry lung) of Japanese autopsied patients were 0.54, 0.44, and 0.87, respectively. The modal values were 0.3, 0.3 and 0.5, respectively. Each of the PAH concentrations was highly correlated with the others (r > 0.83). PAH concentrations in the lungs showed age-related increases with low correlation-coefficient values. BaP, BkF and BghiP concentrations in lungs of various subgroups were in the following order: male > female; and lung cancer > all cancers > non-cancer among male not female group. Only BghiP concentration in the lungs of the male smoker group is significantly higher (P < 0.10) than that of the male non-smoker group. Even among non-smoker groups, PAH concentrations in the lungs of male group were significantly higher than those of female group."

Seto - Arch Environ Contam Toxicol 1993 abstract / PubMed
Seto / Arch Environ Contam Toxicol 1993 full article / UCSF (pdf, 6 pp)

Benzo[a]pyrene 7,8-diol-9,10-epoxide

Benzo[a]pyrene 7,8-diol-9,10-epoxide is metabolized from benzo[a]pyrene

"Benzo[a]pyrene is metabolized to approximately 20 primary and secondary oxidized metabolites and to a variety of conjugates (see HSDB [366] information immediately below). Several metabolites can induce mutations, transform cells and/or bind to cellular macromolecules; however, only a 7,8-diol-9,10-epoxide is presently considered to be an ultimate carcinogenic metabolite [847]." {Environmental Contaminants Encyclopedia. Benzo[a]pyrene (BAP) Entry. July 1, 1997. Compilers/Editors Roy J. Irwin, National Park Service.)

Erwin, 1997 / National Park Service (pdf, 73pp)

Anti-smokers falsely blame benzo[a]pyrene 7,8-diol-9,10-epoxide for "tobacco-induced" lung cancer

High DNA damage by benzo[a]pyrene 7,8-diol-9,10-epoxide in bronchial epithelial cells from patients with lung cancer: comparison with lung parenchyma. Rojas M, Marie B, Vignaud JM, Martinet N, Siat J, Grosdidier G, Cascorbi I, Alexandrov K.Cancer Lett. 2004 Apr 30;207(2):157-63. They claim that "The high formation of BDPE-N(2)-dG adducts in bronchial epithelial cells and investigations showing that the profile of mutations induced by BPDE in these cells is similar to that seen in the p53 gene isolated from human lung tumors implicates benzo[a]pyrene as important carcinogen in tobacco-induced lung cancer in human beings." However, the levels found in smokers and non-smokers overlapped, with "4-fold interindividual differences in the DNA adduct levels in the range of 36.5-175.4 BPDE-N(2)-dG adducts/10(8) nucleotides in smokers (mean: 84.7+/-38.4; n = 13) and 3-fold differences in the range of 19.7-62.4 in non-smokers (mean: 37.6+/-22.2; n = 3," which is not consistent with the vastly greater difference in exposure to tobacco smoke between smokers and non-smokers. Their conclusion also ignores the key fact that, among both smokers and non-smokers, food is the largest source of BaP from which benzo[a]pyrene 7,8-diol-9,10-epoxide is metabolized. In the "Discussion," they employ the typical anti-smoker evasive technique of raising this issue and then dropping it, without examining its implications! They also completely ignore the possibility that infection could influence adduct formation. (And, note that they invoke FORCES's friends, Ernst L. Wynder and S.S. Hecht of the American Health Foundation, as authority for their claim that BAP and BPDE are "involved in the aetiology of lung cancer.")

Rojas - Cancer Lett 2004 full article / EU Lung Cancer Partnership (pdf, 7pp)

Estimating preventable fractions of disease caused by a specified biological mechanism: PAHs in smoking lung cancers as an example. LA Cox Jr, E Sanders. Risk Anal 2006 Aug;26(4):881-892. "We illustrate the approach by estimating an upper bound on the contribution to lung cancer risk made by a specific, much-discussed causal pathway that links smoking to a polycyclic aromatic hydrocarbon (PAH) (specifically, benzo(a)pyrene diol epoxide-DNA) adducts at hot spot codons at p53 in lung cells. The result is a surprisingly small preventable fraction (of perhaps 7% or less) for this pathway, suggesting that it will be important to consider other mechanisms and non-PAH constituents of tobacco smoke in designing less risky tobacco-based products."

Cox - Risk Anal 2006 abstract / PubMed

Anti-smokers try to blame BaP for breast cancer

Chemically induced DNA hypomethylation in breast carcinoma cells detected by the amplification of intermethylated sites. B Sadikovic, TR Haines, DT Butcher, DI Rodenhiser. Breast Cancer Res. 2004; 6(4): R329–R337. As usual, the anti-smoker charlatans ignore key facts including vastly higher exposure to BaP from food versus smoking, and the possible role of infection. Epstein-Barr virus has been implicated as a possible cause of breast cancer.

Sadikovic - Breast Cancer Res 2004 full article / PubMed Central

CpG Methylation of Human Papillomavirus Type 16 DNA in Cervical Cancer Cell Lines and in Clinical Specimens: Genomic Hypomethylation Correlates with Carcinogenic Progression. V Badal, LS Chuang, EH Tan, S Badal, LL Villa, CM Wheeler, BF Li, HU Bernard. J Virol 2003 Jun;77(11):6227-6234. "In 81 patients from two different cohorts, the LCR and the E6 gene of HPV-16 DNA were found to be hypermethylated in 52% of asymptomatic smears, 21.7% of precursor lesions, and 6.1% of invasive carcinomas. This suggests that neoplastic transformation may be suppressed by CpG methylation, while demethylation occurs as the cause of or concomitant with neoplastic progression... Two speculative and opposing views might explain this observation. The cell may have an antiviral defense that senses viral DNA as foreign and targets it for transcriptional repression. Alternatively, DNA methylation may be yet another example of the numerous strategies developed by HPVs that favor a subclinical, long-term maintenance of the viral infection. Such a model would be reminiscent of the life cycle of Epstein-Barr virus, which includes DNA methylation-dependent silencing of a specific promoter during one form of latency."

Badal - J Virol 2003 full article
Badal - J Virol 2003 full article / PubMed Central

See also:

The Lie That p53 Mutations Are the Mechanism Behind Lung Cancer

Formaldehyde

Reevaluation of mortality risks from nasopharyngeal cancer in the formaldehyde cohort study of the National Cancer Institute. GM Marsh, OA Youk. Regul Toxicol Pharmacol 2005 Aug;42(3):275-283. "CONCLUSIONS: Overall, our reanalysis provided little evidence to support NCI's suggestion of a causal association between formaldehyde exposure and mortality from NPC. NCI's conclusion of a possible causal association was driven heavily by anomalous findings in one study plant (Plant 1). An independent and larger study of Plant 1 by the current authors concluded the NPC excess was not associated with formaldehyde exposure. Our findings cast considerable additional uncertainty regarding the validity of NCI's suggested causal association."

Marsh - Regul Toxicol Pharmacol 2005 abstract / PubMed

"[A]ll types of NPC, regardless of histological type or differentiation contain clonal episomal EBV genomes, express specific EBV genes and are a clonal expansion of EBV-infected cells." And studies which ignore it are defective and will falsely blame irrelevant, non-causal associations.

Epstein-Barr Virus Causes Nasopharyngeal Cancer

Mortality from lymphohematopoietic malignancies among workers in formaldehyde industries: the National Cancer Institute Cohort. LE Beane Freeman, A Blair, JH Lubin, PA Stewart, RB Hayes, RN Hoover, M Hauptmann. J Natl Cancer Inst 2009 May 20;101(10):751-761. 25,619 workers employed at one of 10 formaldehyde-using or formaldehyde-producing plants before 1966. "When follow-up ended in 2004, there were statistically significant increased risks for the highest vs lowest peak formaldehyde exposure category (> or =4 parts per million [ppm] vs >0 to <2.0 ppm) and all lymphohematopoietic malignancies (RR = 1.37; 95% CI = 1.03 to 1.81, P trend = .02) and Hodgkin lymphoma (RR = 3.96; 95% CI = 1.31 to 12.02, P trend = .01). Statistically nonsignificant associations were observed for multiple myeloma (RR = 2.04; 95% CI = 1.01 to 4.12, P trend > .50), all leukemia (RR = 1.42; 95% CI = 0.92 to 2.18, P trend = .12), and myeloid leukemia (RR = 1.78; 95% CI = 0.87 to 3.64, P trend = .13). " "The Occupational Safety and Health Administration (OSHA) estimated that in 1995 approximately 2.1 million people in the United States were exposed to formaldehyde in the workplace;" exposure of the general population is lower.

Beane Freeman - J Natl Cancer Inst 2009 full article / PubMed Central

A large proportion of Hodgkin lymphoma is caused by Epstein-Barr virus infection, which is more common among poorer people, and this study is defective because it did not take EBV infection into account.

Epstein-Barr Virus Causes Lymphomas

IARC and NIEHS / NTP Charlatans Blame Formaldehyde for Cancers Caused by EBV

In its 2006 evaluation of formaldehyde and nasopharyngeal carcinoma, the International Agency for Research on Cancer (IARC) had no studies at all which included EBV. Nevertheless, they proclaimed that "The Working Group considered it improbable that all of the positive findings for nasopharyngeal cancer that were reported from the epidemiological studies, and particularly from the large study of industrial workers in the USA, could be explained by bias or unrecognized confounding effects," and that "the results of the study of industrial workers in the USA, supported by the largely positive findings from other studies, provided sufficient epidemiological evidence that formaldehyde causes nasopharyngeal cancer in humans."

In its 2012 update on formaldehyde, there was only one - and it found a whopping 170-fold increased risk from EBV, compared with a puny adjusted RR of 1.6 (95% CI = 0.91-2.9) for formaldehyde, which is non-significant! They claimed that “The association between formaldehyde and NPC was stronger in analyses restricted to EBV seropositive individuals (RR = 2.7; 95% CI = 1.2-5.9). However, no dose response was observed with increasing duration or cumulative use." But as an occupational exposure study, it was pathetic (and all too typical). There was no actual measurment of exposure, only a guess by an industrial hygienist based on job titles. Yet the the IARC ignored that 170-fold risk, and again proclaimed, "It is concluded that occupational exposure to formaldehyde causes nasopharyngeal cancer in humans. The Working Group noted that it was unlikely that confounding or bias could explain the observed association." (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Formaldehyde. Volume 100F, 2012.) They're either imbeciles or corrupt, and because they're purported to be experts, the former excuse is not open to them.

Formaldehyde. Volume 100F, 2012 / IARC (pdf, 36 pp)

It was likewise with the NTP declaration that formaldehye is a human carcinogen in 2011 (12th Report on Carcinogens, unchanged since). None of the so-called "experts," who unanimously rubberstamped this thing, even has any background in the role of infection in the relevant diseases. And, the NTP has never acknowledged EBV to be a human carcinogen, although the IARC did so way back in 1997. They also ignored the role of HPV in sinonasal cancer. The NTP only acknowledged HPV as a human carcinogen in 2004, while the IARC designated it as such in 1995. (Formaldehyde. Report on Carcinogens, Thirteenth Edition, U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 2014).

Formaldehyde, 13th Report on Carcinogens / National Institute of Environmental Health Sciences (pdf, 11 pp)

Their SOLE reference on EBV is a study which claimed to find a risk among current smokers of more than 60 pack-years. However, the only EBV-related parameter considered was "diagnosis of infectious mononucleosis," which is associated with EBV infection later in life (whereas EBV infection early in life is characteristic of areas where NPC is endemic, and also occurs earlier among smokers, for socioeconomic reasons). They blew off the importance of EBV in this fashion: "A link between nasopharyngeal carcinoma and infection with the EBV is well documented. However, infection with EBV is a worldwide phenomenon; serological evidence points to its almost ubiquitous presence. Thus, even though the EBV infection appears to be a necessary factor in the development of many nasopharyngeal carcinomas, it is also clear that additional cofactors are required before a malignancy is expressed." This is the standard blow-off of health fascist quacks. The supposed "additional cofactors" of interest to them include human genes but not EBV genes, and "lifestyle" bogeymen which do not include infection with EBV early in life, plus more frequent exposures thereafter.

EBV & Socioeconomic Status

An estimate of the supposed "expert qualifications" of the NTP Formaldehyde Panel, based on published studies showing their experience with viruses:

McMartin KE 0/80 re any virus
Akbar-Khanzadeh F 0/26 re any virus; has also done anti-smoking studies
Boorman GA 3/191, re any virus (Covance pathologist) mouse hepatitis virus, HCV transgenic mice, 2
DeRoos A 0/4 re any virus
Demers P 0/193 re any virus
Peterson LA, @Mayo 0/7 re any virus; has also done anti-smoking studies
Rappaport SM 0/177 re any virus
Richardson DB 0/82 re any virus
Sanderson WT 0/53 re any virus
Sandy MS 0/28 re any virus
-------------------------------------------------------------------------------------------
841 studies, 3 re virus (in mice, none re EBV or HPV which are relevant to human disease)

Technical Experts to the Panel (Non-voting)
Freeman LB 0/13 re any virus
DeVito M 0/70 re any virus
Elmore SA 2/22, chikungunya virus in mice, influenza in raccoons
Zhang L @Berkeley 1/75, dengue virus in mice
-----------------------------------------------------------------
180 studies, 3 re virus in animals, none re EBV or HPV which are relevant to human disease

Quoth the charlatans at NTP: "The expert panel discussed all of the sections of the draft background document on formaldehyde, including the adequacy and clarity of information, and offered specific proposed revisions to be made to the document. The panel voted 9 yes/0 no to accept the draft background document (with proposed changes) and that it is adequate for drawing conclusions about the carcinogenicity of formaldehyde exposure and for applying the RoC listing criteria." (Peer Review of the Draft Background Document on Formaldehyde, Nov. 2-4, 2009.)

Peer Review of the Draft Background Document on Formaldehyde, 2009 / NIEHS (pdf, 27 pp)

The role of industry has always been to meekly shovel out money to their worst enemies, and never question their methods. "Du Pont has an epidemiological surveillance program, under which 70 company sites are periodically analyzed to ascertain whether the employees have a significant excess of any type of cancer. If necessary, additional studies are done to determine whether the excess is work-related. Cohort studies of employees who have been exposed to known or suspected carcinogens are conducted. Du Pont has maintained a cancer registry since 1956, and company employees are participating in an NCI cytology screening program for bladder cancer. It is also collaborating in the formaldehyde study being conducted by the NCI and the Formaldehyde Institute." The major unions pour funds into the pockets of quacks, too. (National Cancer Program 1982. Director's Report and Annual Plan, Fy 1984-1988. Nonprofit Organizations, p. 27.)

National Cancer Program 1982 / UCSF (pdf, 31 pp)

Letter from Cal Dooley, President and CEO of the American Chemistry Council, to The New York Times, uttering namby-pamby platitudes about "confidence in the conclusions," dubious speculation about "putting jobs at risk," but no actual crtiticism of the science whatsoever. (Doubt on Cancer Report. New York Times, Oct. 14, 2012.) This is exactly the kind of drivel that reassures the public that the opponents of the chemical industry have done nothing wrong, and encourages their followers to self-righteously smear that the industry only cares about its own profits.

Doubt on Cancer Report / New York Times, 2012

Official OSHA Policy on Secondhand Smoke

"Because the organic material in tobacco doesn't burn completely, cigarette smoke contains more than 4,700 chemical compounds. Although OSHA has no regulation that addresses tobacco smoke as a whole, 29 CFR 1910.1000 Air contaminants, limits employee exposure to several of the main chemical components found in tobacco smoke. In normal situations, exposures would not exceed these permissible exposure limits (PELs), and, as a matter of prosecutorial discretion, OSHA will not apply the General Duty Clause to ETS." (02/24/2003 - Reiteration of Existing OSHA Policy on Indoor Air Quality: Office Temperature/Humidity and Environmental Tobacco Smoke. Standard Number: 1910.1000.)

Reiteration of Existing OSHA Policy on Indoor Air Quality / OSHA

"Tobacco-Specific" [sic] Nitrosamines

The National Toxicology Program (NTP)

N'-Nitrosonornicotine. CAS No. 16543-55-8. Report on Carcinogens, Eleventh Edition. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program. Announcement of the draft in the Federal Register was on Nov. 13, 2007. For NNN: "No adequate human studies of the relationship between exposure to N-nitrosonornicotine and human cancer have been reported (IARC 1978, 1985, 1987)." NNK and N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) were not listed among the carcinogens. (Links died.)

N'-Nitrosonornicotine (NNN), CAS No. 16543-55-8, p. 320: "No epidemiological studies were identified that evaluated the relationship between human cancer and exposure specifically to N-nitrosonornicotine." N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) were not listed among the carcinogens. (Report on Carcinogens, Twelfth Edition, 2011.)

N'-Nitrosonornicotine (NNN), CAS No. 16543-55-8: "No epidemiological studies were identified that evaluated the relationship between human cancer and exposure specifically to N‑nitrosonornicotine." 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) CAS No. 64091-91-4: "No epidemiological studies were identified that evaluated the relationship between human cancer and exposure specifically to NNK." N′-nitrosoanatabine (NAT), N′-nitrosoanabasine (NAB), and 4-(Methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL) were not listed among the carcinogens. (Report on Carcinogens, 13th Edition, 2014.)

N-Nitrosamines: 15 Listings, 13th Edition / NTP, NIEHS, NIH (pdf, 23 pp)
Report on Carcinogens, 13th Edition, 2014 / NTP, NIEHS, NIH (zip)
Main Page, 13th Report on Carcinogens / NTP, NIEHS, NIH

Q: "Aren’t the TSNA actually the same as any other nitrosomine?" R: “Actually the same” only in the sense that all they have are animal studies and no human ones. And the types of cancers they claim the nitrosamines cause, such as nasal carcinomas, are in HUMANS known to be caused by Epstein-Barr virus, with some others by HPV. So it’s automatically invalid to extrapolate to humans, as they’ve done.

The International Agency for Research on Cancer (IARC)

It states that "There is inadequate evidence in humans for the carcinogenicity of N′-nitrosonornicotine (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNN). There is sufficient evidence in experimental animals for the carcinogenicity of 4-(methylnitrosamino)-1-(3-py r idyl)-1-butanone. There is sufficient evidence in experimental animals for the carcinogenicity of N′-nitrosonornicotine." Nevertheless, despite "inadequate evidence" in humans, they proclaimed that "4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and N′-nitrosonornicotine are carcinogenic to humans (Group 1)." (Monograph 100E, N′-Nitrosonornicotine and and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. IARC, 2012.)

Monograph 100E, NNN and NNK 2012 / IARC (pdf, 14 pp)

As usual with monographs on purported chemical carcinogens, the participants' collective experience relating to the role of viruses in human cancers could be jotted on a post-it note with plenty of space left over. Worst of all, SS Hecht, who has been pushing to have NNN and NNK proclaimed to be human carcinogens since the 1970s, was one of the participants in this monograph. He was also the head of the lab in both of the human studies of NNN and NNK that were nevertheless deemed inadequate, as well as a co-author of most of the animal studies cited! (List of Participants. Volume 100E (2012) Personal Habits and Indoor Combustions.)

List of Participants. Volume 100E (2012) Personal Habits and Indoor Combustions / IARC (pdf, 6 pp)

Deliberate Fraud By the National Institute of Environmental Health Sciences

The NIEHS has been induced to include human papillomaviruses among its list of known carcinogens. (Report on Carcinogens, Eleventh Edition. National Toxicology Program.) However, other known carcinogenic viruses and bacteria are not included, such as Epstein-Barr Virus, a known cause of nasopharyngeal cancers and lymphomas, and hepatitis viruses B and C, which cause well over 90% of all liver cancers. The vast majority of their assessments of carcinogenicity are based on studies that considered only exposure to the chemicals in question, which ignored the fact that working class people are more likely, for socioeconomic reasons, to have been exposed to these carcinogenic viruses. Yet nowhere is there any mention of the probability of confounding. This means that the NIEHS falsely blames a multitude of chemicals for cancers that are really caused by infection. Other scientifically corrupt agencies such as the National Cancer Institute and the Surgeon General employ the supposed authority of this list to spread lies and defamations about smoking and secondhand smoke.

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cast 01-04-16