Molecular dosimetry of aflatoxin-N7-guanine in human urine obtained in The Gambia, West Africa.
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 micrograms 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Groopman
J D
JD
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland 21205.
Hall
A J
AJ
Whittle
H
H
Hudson
G J
GJ
Wogan
G N
GN
Montesano
R
R
Wild
C P
CP
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000652:urine; D000348:Aflatoxins / Q000009:adverse effects / Q000032:analysis* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology; D002846:Chromatography, Affinity; D002851:Chromatography, High Pressure Liquid; D004032:Diet / Q000009:adverse effects; D004034:Diet Surveys; D004784:Environmental Monitoring / Q000379:methods* / Q000592:standards; D004797:Enzyme-Linked Immunosorbent Assay; D062665:Epidemiological Monitoring; D005069:Evaluation Studies as Topic; D005260:Female; D005504:Food Analysis; D005714:Gambia / Q000453:epidemiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006509:Hepatitis B / Q000097:blood / Q000150:complications / Q000652:urine*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006801:Humans; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000348:Aflatoxins; D006514:Hepatitis B Surface Antigens; D006147:Guanine; C028319:2,3-dihydro-2-(N(7)-guanyl)-3-hydroxyaflatoxin B1; D016604:Aflatoxin B1