Journal Article

Elevated <i>HPRT</i> mutation frequencies in aflatoxin-exposed residents of Daxin, Qidong County, People's Republic of China

Sophia S. Wang, J.Patrick O'Neill, Geng-Sun Qian, Yu-Rong Zhu, Jia-Bin Wang, Haroutune Armenian, Audrey Zarba, Jia-Sheng Wang, Thomas W. Kensler, Neal F. Cariello, John D. Groopman and James A. Swenberg

in Carcinogenesis

Volume 20, issue 11, pages 2181-2184
Published in print November 1999 | ISSN: 0143-3334
Published online November 1999 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/20.11.2181
Elevated HPRT mutation frequencies in aflatoxin-exposed residents of Daxin, Qidong County, People's Republic of China

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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.

Keywords: 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.

Journal Article.  3502 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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