Molecular Dosimetry of Aflatoxin-N7-guanine In Human Urine Obtained in The Gambia, West Africa

John D. Groopman, Andrew J. Hall, Ruggero Montesano, Christopher P. Wild, Hilton Whittle, Geoffrey J. Hudson, Gerald N. Wogan

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatocellular carcinoma is one of the major human cancers, causing at least 250,000 deaths each year. Two of the major risk factors for this disease are aflatoxin exposure and hepatitis B virus. This study was undertaken to explore the relationship between dietary exposure to aflatoxins and the excretion of the major aflatoxin-DNA adduct and other metabolites into the urine of chronically exposed people who were either hepatitis B virus surface antigen-positive or -negative. The diets of 20 individuals, 10 males and 10 females, with ages ranging from 15 to 56 years, were monitored for 1 week, and aflatoxin intake levels were determined for each day. Starting on the fourth day, total 24-h urines were consecutively obtained for 4 days. The subjects were generally paired for hepatitis B virus status. Preparative monoclonal antibody affinity chromatography/high-performance liquid chromatography and competitive enzyme-linked immunosorbent assays were carried out on each of the urine samples, and the relationship between aflatoxin intake values and the excretion of (a) total aflatoxin metabolites and (b) aflatoxin-N7-guanine (AFB-N7-guanine) was determined. The average intake of total aflatoxins was 12.0 μg for the entire study group during the 1-week collection period. However, there was considerable day-to-day variation in exposures, from a low of zero to a high of 29.6 Mg total aflatoxins/day. Initial efforts to characterize total aflatoxin metabolites in the urine samples were made by competitive enzyme-linked immunosorbent assay. The correlation coefficient for the analysis was 0.65, with P > 0.001. These competitive immunoassays determine a composite representation of the aflatoxin compounds in urine, and a separation method using high-performance liquid chromatography was required to resolve the individual aflatoxin components in urine. High-performance liquid chromatography revealed the preponderance of aflatoxin Gt in many of the urine samples in addition to the oxidative metabolites aflatoxin Pu aflatoxin Q1, and AFB-N7-guanine. One of the objectives of this study was to determine the molecular dosimetry of AFB-N7-guanine in people who were either hepatitis B virus surface antigen-positive or -negative. Comparison of total AFB-N7-guanine excretion in the urine of all subjects over the complete collection period plotted with total aflatoxin B1 exposure in the diet yields a correlation coefficient of 0.82 with P > 0.0001. Separation of the population into hepatitis B virus carriers and noncarriers revealed no difference in aflatoxin-DNA adduct levels in urine for a given dietary exposure.

Original languageEnglish (US)
Pages (from-to)221-227
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume1
Issue number3
StatePublished - 1992

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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