Aflatoxin Bl (AFBl) is one of the most potent liver carcinogens known for experimental animals. This chemical is also present in the environment as a result of mold related spoilage of foods and commodities. Consumption of these foods results in high intake of AFBl by people living in many regions of Asia and Africa. A number of researchers have used classic epidemiological methods to examine the possible causal relationship between AFBl in the diet and liver cancer. While strong associations between AFBl exposure and liver cancer have been found, new technologies have only recently become available to monitor individual exposure and metabolism of aflatoxin Bl in people. These methods will facilitate the dissection of the role of viral agents, such as hepatitis B, from aflatoxins in the etiology of liver cancer. The development of biomarkers to assess the exposure to aflatoxin will help in efforts to limit the potential risk in human populations. In the following proposed study we will examine both seasonal and annual variabilities in aflatoxin intake, metabolism, urinary and albumin disposition in people living in the Gambia, West Africa who are at high risk to develop liver cancer. These studies will systematically probe the correspondence between dietary intake of aflatoxins with biological markers, such as excreted AFB-DNA adducts, oxidative metabolites in urine, aflatoxin Ml in human milk and covalently bound aflatoxin to serum albumin, to determine which of these markers have utility for non-invasively assessing the exposure status of people at high risk for liver cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01CA048409-01
Application #
3549174
Study Section
(SRC)
Project Start
1988-09-15
Project End
1992-07-31
Budget Start
1988-09-15
Budget End
1989-07-31
Support Year
1
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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Groopman, J D; Roebuck, B D; Kensler, T W (1994) Carcinogen-DNA and protein adducts as intermediate biomarkers for human chemoprotection trials. Adv Exp Med Biol 354:149-60
Wild, C P; Jansen, L A; Cova, L et al. (1993) Molecular dosimetry of aflatoxin exposure: contribution to understanding the multifactorial etiopathogenesis of primary hepatocellular carcinoma with particular reference to hepatitis B virus. Environ Health Perspect 99:115-22
Hollstein, M C; Wild, C P; Bleicher, F et al. (1993) p53 mutations and aflatoxin B1 exposure in hepatocellular carcinoma patients from Thailand. Int J Cancer 53:51-5
Groopman, J D; Wild, C P; Hasler, J et al. (1993) Molecular epidemiology of aflatoxin exposures: validation of aflatoxin-N7-guanine levels in urine as a biomarker in experimental rat models and humans. Environ Health Perspect 99:107-13
Wild, C P; Fortuin, M; Donato, F et al. (1993) Aflatoxin, liver enzymes, and hepatitis B virus infection in Gambian children. Cancer Epidemiol Biomarkers Prev 2:555-61
Sheabar, F Z; Groopman, J D; Qian, G S et al. (1993) Quantitative analysis of aflatoxin-albumin adducts. Carcinogenesis 14:1203-8
Groopman, J D; Hall, A J; Whittle, H et al. (1992) Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa. Cancer Epidemiol Biomarkers Prev 1:221-7
Allen, S J; Wild, C P; Wheeler, J G et al. (1992) Aflatoxin exposure, malaria and hepatitis B infection in rural Gambian children. Trans R Soc Trop Med Hyg 86:426-30
Wild, C P; Shrestha, S M; Anwar, W A et al. (1992) Field studies of aflatoxin exposure, metabolism and induction of genetic alterations in relation to HBV infection and hepatocellular carcinoma in The Gambia and Thailand. Toxicol Lett 64-65 Spec No:455-61

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