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.
|Number of pages
|Cancer Epidemiology Biomarkers and Prevention
|Published - 1992
ASJC Scopus subject areas