The aim of this Program Project is to increase understanding of the mechanisms of chemical carcinogenesis in human. Mechanisms will be studied directly in human who have exposures to known environmental carcinogens: cigarette smoke (whose constituents include ethylene oxide, styrene, 4- aminobiphenyl, polycyclic aromatic hydrocarbons or PAHs) and foundry air (which contains high levels of PAHS). All of the laboratories within he Program will evaluate biologic samples from the same individuals, using biologic markers to assess the association between potential markers of genetic susceptibility (P1-450 induction, AHH activity and glutathione-S- transferase activity) on induction of procarcinogenic effects (carcinogen- DNA and -protein adducts, gene mutations at the hprt locus and activation of c-ras, c-myc and c-fes proto-oncogenes). In contrast to these mechanisms of genetic toxicity, associated with cancer initiation and possibly other stages in the carcinogenic process, little is known about the mechanisms involved in tumor promotion. Because these are important determinants of individual cancer risk, novel methods will be developed to measure effects of certain non-genotoxic agents and tumor promotors on the activity of our model populations, who also experiences high exposure to known tumor promotors, will be studied. Thus, the combined resources of the Program will provide comprehensive data on a broad spectrum of events and processes in human carcinogenesis. They will also help to clarify the nature and significance of interindividual variability in response to carcinogens. These studies are an essential prerequisite to incorporating biologic markers into quantitative risk assessment and epidemiologic studies of cancer causation. Our goal, at the end of 5 years, is to carry our a longitudinal epidemiologic study, in order to determine the ability of biologic markers to predict individual risk of cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES005294-03
Application #
3095966
Study Section
Environmental Health Sciences Review Committee (EHS)
Project Start
1989-12-01
Project End
1994-11-30
Budget Start
1991-12-01
Budget End
1992-11-30
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Mooney, L A; Perera, F P; Van Bennekum, A M et al. (2001) Gender differences in autoantibodies to oxidative DNA base damage in cigarette smokers. Cancer Epidemiol Biomarkers Prev 10:641-8
Whyatt, R M; Perera, F P; Jedrychowski, W et al. (2000) Association between polycyclic aromatic hydrocarbon-DNA adduct levels in maternal and newborn white blood cells and glutathione S-transferase P1 and CYP1A1 polymorphisms. Cancer Epidemiol Biomarkers Prev 9:207-12
Whyatt, R M; Santella, R M; Jedrychowski, W et al. (1998) Relationship between ambient air pollution and DNA damage in Polish mothers and newborns. Environ Health Perspect 106 Suppl 3:821-6
Whyatt, R M; Bell, D A; Jedrychowski, W et al. (1998) Polycyclic aromatic hydrocarbon-DNA adducts in human placenta and modulation by CYP1A1 induction and genotype. Carcinogenesis 19:1389-92
Mooney, L A; Bell, D A; Santella, R M et al. (1997) Contribution of genetic and nutritional factors to DNA damage in heavy smokers. Carcinogenesis 18:503-9
Dickey, C; Santella, R M; Hattis, D et al. (1997) Variability in PAH-DNA adduct measurements in peripheral mononuclear cells: implications for quantitative cancer risk assessment. Risk Anal 17:649-56
Perera, F P; Mooney, L A; Dickey, C P et al. (1996) Molecular epidemiology in environmental carcinogenesis. Environ Health Perspect 104 Suppl 3:441-3
Mooney, L A; Perera, F P (1996) Application of molecular epidemiology to lung cancer chemoprevention. J Cell Biochem Suppl 25:63-8
Perera, F P; Blaner, W; Mooney, L V (1996) Molecular epidemiologic methods in cancer chemoprevention. Eur J Cancer Prev 5 Suppl 2:19-25
Savela, K; Kohan, M J; Walsh, D et al. (1996) In vitro characterization of DNA adducts formed by foundry air particulate matter. Environ Health Perspect 104 Suppl 3:687-90

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