Cigarette smoking is causally associated with cancer of the lung, larynx and esophagus and increases the risk for cancer of the pancreas, kidney and urinary bladder and, likely, the cervix. Pipe and cigar smoking which increases the risk for lung cancer to a lesser degree, is causally associated with cancer of the larynx, oral cavity and esophagus. Exposure to environmental tobacco smoke (ETS) gives rise to some risk of cancer. Snuff- dipping is causatively related to cancer of the oral cavity and pharynx; chewing of tobacco may be associated with oral cancer. Betel quid chewing with tobacco is carcinogenic to humans, without tobacco it is less so. Cigarette mainstream smoke (MS) and its particulate matter induce benign and malignant tumors in laboratory animals. Bioassay data on the carcinogenic activity of sidestream smoke (SS), ETS and snuff, chewing tobacco, and betel quid are needed. To elucidate problems in tobacco carcinogenesis, we propose I) continuation of the development of sensitive quantitative assays for globin- and DNA-adducts with tobacco-specific N- nitrosamines (TSNA) and application to analysis of blood samples, exfoliated oral cells and oral cavity punch biopsy samples from smokers, passive smokers and snuff-dippers; II) refinement of analytical methods for TSNA and synthesis and bioassays of newly identified TSNA; application of appropriate methods to MS, SS, ETS and snuff profile analysis; study of the endogenous formation of nitrosamines in smokers and chewers; III) delineation of the formation of 3-(methylnitrosamino) propionitrile (MNPN) during betel quid chewing, and of factors that influence the formation of areca- and tobacco-specific nitrosamines; study of the binding of MNPN metabolites to DNA, of the metabolism of the betel quid alkaloid, arecoline, development of an immunoassay for its major metabolite and application to saliva, blood and urine analyses of betel quid chewers; IV) determination of aromatic amines and their metabolites in the urine of smokers, passive smokers and nonsmokers and development of an immunoassay for o-toluidine in urine; V) elucidation of the chemical nature of biologically active flavor components in the smoke of cigarettes, and in snuff; VI) bioassay for carcinogenicity of SS and studies on the uptake of SS and ETS by active and passive smokers; analysis of biological fluids of passive smokers for tobacco-specific markers and determination of such markers in stored biological fluids of presumed nonsmokers with lung cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
3P01CA029580-11S1
Application #
3093314
Study Section
Special Emphasis Panel (SRC (15))
Project Start
1981-06-15
Project End
1993-01-31
Budget Start
1991-07-15
Budget End
1993-01-31
Support Year
11
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Institute for Cancer Prevention
Department
Type
DUNS #
City
Valhalla
State
NY
Country
United States
Zip Code
10595
Boffetta, Paolo; Jayaprakash, Vijayvel; Yang, Ping et al. (2011) Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO). Cancer Causes Control 22:73-9
Mitacek, Eugene J; Brunnemann, Klaus D; Suttajit, Maitree et al. (2008) Geographic distribution of liver and stomach cancers in Thailand in relation to estimated dietary intake of nitrate, nitrite, and nitrosodimethylamine. Nutr Cancer 60:196-203
Prokopczyk, Bogdan; Hoffmann, Dietrich; Bologna, Matthew et al. (2002) Identification of tobacco-derived compounds in human pancreatic juice. Chem Res Toxicol 15:677-85
Mitacek, E J; Brunnemann, K D; Suttajit, M et al. (1999) Exposure to N-nitroso compounds in a population of high liver cancer regions in Thailand: volatile nitrosamine (VNA) levels in Thai food. Food Chem Toxicol 37:297-305
Prokopczyk, B; Cox, J E; Hoffmann, D et al. (1997) Identification of tobacco-specific carcinogen in the cervical mucus of smokers and nonsmokers. J Natl Cancer Inst 89:868-73
Stellman, S D; Muscat, J E; Hoffmann, D et al. (1997) Impact of filter cigarette smoking on lung cancer histology. Prev Med 26:451-6
Koppang, N; Rivenson, A; Dahle, H K et al. (1997) A study of tobacco carcinogenesis, LIII: carcinogenicity of N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in mink (Mustela vison). Cancer Lett 111:167-71
Hoffmann, D; Djordjevic, M V (1997) Chemical composition and carcinogenicity of smokeless tobacco. Adv Dent Res 11:322-9
Stellman, S D; Muscat, J E; Thompson, S et al. (1997) Risk of squamous cell carcinoma and adenocarcinoma of the lung in relation to lifetime filter cigarette smoking. Cancer 80:382-8
Hoffmann, D; Djordjevic, M V; Hoffmann, I (1997) The changing cigarette. Prev Med 26:427-34

Showing the most recent 10 out of 114 publications