Molecular Dosimetry of Urinary Aflatoxin-DNA Adducts in People Living in Guangxi Autonomous Region, People's Republic of China

John D. Groopman, Zhu Jiaqi, Paul R. Donahue, Anthony Pikul, Zhang Lisheng, Chen Jun-shi, Gerald N. Wogan

Research output: Contribution to journalArticle

Abstract

Hepatocellular carcinoma is one of the five leading human cancers causing at least 250,000 deaths each year. One of the major risk factors for this disease is exposure to dietary anatoxins, and the development of appropriate molecular dosimetry biomarkers would facilitate the identification of individuals at risk. This study was undertaken to explore the relationship between dietary intake of anatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people. The following protocol was developed for this investigation in Guangxi Autonomous Region, People's Republic of China, where the diets of 50 males and 12 females (ages, 25-64 years) were monitored for 1 week and anatoxin intake levels determined each day. Starting on the fourth day, total urine volumes were obtained in consecutive 12-h fractions for 3 or 4 days. High performance liquid chromatography and competitive radioimmunoassay analyses were done on each of the urine samples, and the relationships between excretion of total aflatoxin metabolites, aflatoxin-AT-guanine, anatoxin Mt, anatoxin Pi, and aflatoxin B,, and aflatoxin B, intake values were determined. The average intake of aflatoxin B, by men was 48.4 Mg/day, giving a total mean exposure during the study period of 276.8 ng. The average daily intake by women was 77.4 Mg/day, resulting in a total average exposure during the 7-day period of 542.6 Mg aflatoxin B,. Initial efforts to characterize aflatoxin metabolites in urine samples were with an analysis by competitive radioimmunoassay. The analysis by linear regression of the association between aflatoxin Bi intake/day and total aflatoxin me-tabolite excretion/day showed a correlation coefficient of only 0.26. These findings stimulated the immunoaffinity/analytical high performance liquid chromatography analysis for individual metabolites. When the data were analyzed by linear regression analysis, the aflatoxin AT-guanine excretion and aflatoxin Bt intake from the previous day showed a correlation coefficient of 0.65 and P < 0.000001. Similar analysis for aflatoxin Mi resulted in a correlation coefficient of 035 and P < 0.00001, whereas there was no positive statistical association between exposure in the diet and aflatoxin Pi excretion, despite aflatoxin P(being quantitatively a major metabolite. Analysis of the total aflatoxin-AT-gtianine excretion in the urine during the complete collection period plotted against the total aflatoxin B, exposure in the diet for each of the individuals, smoothing the day to day variations, revealed a correlation coefficient of 0.80 and P < 0.0000001. Given this analysis, it is clear that a summation of excretion and exposure status provides a stronger association between exposure and a molecular dosimetry marker than was seen in prior statistical analyses. These findings support the concept that quantitation of the aflatoxin-N7-guanine adduct in urine is a good biomarker for aflatoxin Bi exposures.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalCancer Research
Volume52
Issue number1
StatePublished - Jan 1992

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Groopman, J. D., Jiaqi, Z., Donahue, P. R., Pikul, A., Lisheng, Z., Jun-shi, C., & Wogan, G. N. (1992). Molecular Dosimetry of Urinary Aflatoxin-DNA Adducts in People Living in Guangxi Autonomous Region, People's Republic of China. Cancer Research, 52(1), 45-52.