Carcinogenesis, Vol. 20, No. 11, 2181-2184,
November 1999
© 1999 Oxford University Press
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Elevated HPRT mutation frequencies in aflatoxin-exposed residents of Daxin, Qidong County, People's Republic of China
1 Department of Epidemiology and
2 Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205,
3 Genetics Laboratory, University of Vermont, Burlington, VT 05401,
4 Laboratory of Molecular Carcinogenesis and Mutagenesis, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA,
5 Shanghai Cancer Institute, Shanghai 200032 and
6 Qidong Liver Cancer Institute, Qidong, People's Republic of China
Molecular biomarkers are becoming increasingly important tools to identify people who are at highest risk of developing cancer. For many years we have been studying residents of Qidong County, People's Republic of China, to examine the combined impact of aflatoxin exposure with other risk factors as contributors to the high liver cancer incidence rates in this region. This study was conducted to determine the effects of aflatoxin exposure, as measured by serum aflatoxin–albumin adduct levels, on somatic mutation frequency in the human hypoxanthine guanine phosphoribosyl transferase gene (HPRT). Subjects were assigned as low or high according to a dichotomization around the population mean of aflatoxin–albumin adducts. HPRT mutant frequency was determined in individuals by a T cell clonal assay and the samples were categorized as low or high according to mean values. Separate analyses were also conducted for the small set of hepatitis B virus surface antigen (HBsAg)-positive and the larger set of HBsAg-negative individuals, known risk factors for liver cancer. An odds ratio of 19.3 (95% confidence interval 2.0, 183) was demonstrated for a high HPRT mutation frequency in individuals with high aflatoxin exposure compared with those with low aflatoxin exposure. This association indicates that aflatoxin-induced DNA damage in T lymphocytes, assessed using the validated surrogate albumin adduct markers, leads to increased mutations reflected as elevated HPRT gene mutations. This cross-sectional study suggests the potential use of mutation frequency of the HPRT gene as a long-term biomarker of aflatoxin exposure in high risk populations.
Abbreviations: AFB1, aflatoxin B1; HBsAg, hepatitis B virus surface antigen; HCC, hepatocellular carcinoma; HPRT, hypoxanthine guanine phosphoribosyl transferase gene; PHA, phytohemagglutin; SGPT, serum glutamic pyruvic transaminase; 6-TG, 6-thioguanine.
7 Present address: Glaxo Wellcome Inc., Medicines Safety Evaluation, Building 9, Room 2011, Research Triangle Park, NC 27709, USA
8 To whom correspondence should be addressed at: Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205, USA Email: jgroopma{at}jhsph.edu
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