Tobacco carcinogenicity

Le Marchand, L., Sivaraman, L. et al. (1998). Associations of CYP1A1, GSTM1, and CYP2E1 polymorphisms with lung cancer suggest cell type specificities to tobacco carcinogens. Cancer Res., 58(21), 4858-63. 

Hatsukami DK, Hecht SS, Hennrikus DJ, Joseph AM, Pentel PR (2003) Biomarkers of tobacco exposure or harm application to clinical and epidemiological studies. 25-26 October 2001, Minneapolis, Minnesota. Nicotine Tob Res 5(3) 387-396 Hecht SS (2003) Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat Rev Cancer 3(10) 733-744... 

Harrod SB, Mactutus CF, et al (2004) Sex differences and repeated intravenous nicotine behavioral sensitization and dopamine receptors, Pharmacol Biochem Behav 78(3) 581-592 Hatchell PC, Collins AC (1980) The influence of genotype and sex on behavioral sensitivity to nicotine in mice. Psychopharmacology 71(1) 45 9 Henschke Cl, Miettinen OS (2004) Women s susceptibility to tobacco carcinogens. Lung Cancer 43(l) l-5... 

Henschke Cl, Yip R, et al (2006) Women s susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. JAMA 296(2) 180-184... 

NT005 West, K. A., I. R. Linnoila, S. A. Belinsky, C. C. Harris, and P. A. Dennis. Tobacco carcinogen-induced cellular transformation increases activation of the phosphatidylinositol 3 -kinase/Akt pathway in vitro and in vivo. Cancer Res 2004 64(2) 446-451. 

Tobacco accounts for about 90% of lung cancers. Some tobacco carcinogens induce DNA adducts that are repaired by the nucleotide excision repair (NER) pathway (3). The lowest DNA repair capacity (DRC), measured in peripheral blood lymphocytes by the host cell reactivation assay (HCR), was observed in lung cancer patients who were less than 60 years old, female, or lighter smokers, and in those with a family history of cancer (4,5). 

Hecht, S.S. 2003. Tobacco carcinogens, their biomarkers and tobacco-induced cancer. Nat. Rev. Cancer 3(10) 733-744. 

Nelson HH, Wiencke JK, Gunn L, et al. 1998. Chromosome 3p 14 alterations in lung cancer Evidence the FHIT exon deletion is a target of tobacco carcinogens and asbestos. Cancer Res 58 1804-1807. 

Wiencke JK, Varkonyi A, Thurston SW, et al. Early age at smoking initiation and tobacco carcinogen DNA damage in the lung. J Natl Cancer Inst 1999 91 (7) 614—19. 

The pathogenesis of pulmonaiy tumors induced by a tobacco carcinogen, 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK), and its inhibition by black tea was characterized in female A/J mice (Yang et al., 1997). In this short-term model, the administration of black tea polyphenols (0.3%) through the drinking water significantly inhibited NNK-induced early bronchiolar cell proliferation, as measured... 

Conaway, C., Clifford, Wang, C.X., Pittman, B., Yang, Y.M., Schwartz, J.E., Tian, D., Mclntee, E. J., et al. 2006. Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice. Cancer Research, 65(18), 8548-57. doi 10.1158/0008-5472.CAN-05-0237. 

A large number of polycyclic aromatic hydrocarbons are known Many have been synthesized m the laboratory and several of the others are products of com bustion Benzo[a]pyrene for example is present m tobacco smoke contaminates food cooked on barbecue grills and collects m the soot of chimneys Benzo[a]pyrene is a carcinogen (a cancer causing substance) It is converted m the liver to an epoxy diol that can induce mutations leading to the uncontrolled growth of certain cells... 

The number of clear human epidemiologic studies is small. A total of approximately 50 compounds (c.g., benzene, vinyl chloride) and complex e.xposures (e.g., aluminum production, tobacco smoke) have sufficient data available to permit their classification as human carcinogens. The most potent human carcinogens known, the aflatoxins. are of natural origin. Their presence in food products through infestation by toxin-producing fungi constitute a serious problem in several tropical and subtropical countries. 

The analysis of combustion products presents problems of complexity similar to that of feedstock and raw fuel analysis. A highly complex matrix of aliphatic material often exists (as unburnt fuel in the combustion exhaust), whilst the species of interest, for example, carcinogens or mutagens are often at very low concentrations. A classic example of multidimensional GC is its use in the analysis of flue-cured tobacco essential oil condensate. 

Above the critical temperature and pressure, a substance is referred to as a supercritical fluid. Such fluids have unusual solvent properties that have led to many practical applications. Supercritical carbon dioxide is used most commonly because it is cheap, nontoxic, and relatively easy to liquefy (critical T = 31°C, P = 73 atm). It was first used more than 20 years ago to extract caffeine from coffee dichloromethane, CH2C12, long used for this purpose, is both a narcotic and a potential carcinogen. Today more than 10s metric tons of decaf coffee are made annually using supercritical C02. It is also used on a large scale to extract nicotine from tobacco and various objectionable impurities from the hops used to make beer. 

Another example of enzyme induction involves CYP2E1, which is induced by consumption of ethanol. This is a matter for concern, because this P450 metabohzes certain widely used solvents and also components found in tobacco smoke, many of which are established carcinogens. Thus, if the activity of CYP2E1 is elevated by induction, this may increase the risk of carcinogenicity developing from exposure to such compounds. 

The involvement of tobacco smoke carcinogens in the aetiology of lung cancer is conclusively established, but the role of specific chemical carcinogens as inducers of colorectal cancer is much less clear. Mutagenic pyrolysis products derived from cooked food have come under suspicion as possible... 

CHUNG F L (1999) The prevention of lung cancer induced by a tobacco-specific carcinogen in rodents by green and black tea , Proc Soc Exp Biol Med, 220 (4), 244-8. 

Formation, Occurrence, and Carcinogenicity of iV-Nitrosamines in Tobacco Products... 

Carcinogenicity of NDELA. Our special interest in NDELA as a constituent of tobacco products and as an environmental agent relates to the observation that this nitrosamine induces carcinoma of the liver as well as of the kidney in rats (21,22) and carcinoma of the nasal cavity and papillomas of the trachea in hamsters (23). Recently, Lijinsky reported that NDELA admini-... 

In a study for precursor determination, we stem-fed individual Burley leaves with nicotine-2 - C or nornicotine-2 - C (29). Subsequently, the leaves were air cured, dried and analyzed for NNN and NNN- C. Recovery of the p-activity in the form of NNN- C amounted to 0.009% and 0.007%, respectively of the stem-fed label. This demonstrates that both alkaloids give rise to NNN. More importantly, it points to the fact that the tertiary amine, nicotine, which constitutes 0.5-2.6% of commercial tobaccos (26,27), is the major precursor for the carcinogenic tobacco-specific NNN, while the secondary amine, nornicotine is of lesser importance because it amounts to only 0.005-0.06% in tobacco (Figure 8). 

The alkaloid derived nitrosamines in cigarettes, cigars and pipe tobacco contribute to the quantities of these carcinogens in the smoke because of their partial transfer (32). 

Tobacco Specific N-Nitrosamines Occurrence, Carcinogenicity and Metabolism", ACS Symp. Ser, 1979, 101, 125-152,... 

Brunnemann, K.D. Hoffmann, D. Assessment of the Carcinogenic N-Nitrosodiethanolamine in Tobacco Products and Tobacco Smoke. Submitted. 

Hoffmann, D. Adams, J.D. Carcinogenic Tobacco Specific N-Nitrosamines in Snuff and in the Saliva of Snuff Dippers. Submitted. 

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