Molecular epidemiology of aflatoxin exposures: validation of aflatoxin-N7-guanine levels in urine as a biomarker in experimental rat models and humans.
Human epidemiology and experimental animal data have provided the statistical association and biological information necessary to propose that aflatoxins are risk factors for human liver cancer. As liver cancer causes at least 200,000 deaths per year, prevention measures must be developed to ameliorate this nearly always fatal disease. Preventive strategies will be facilitated by the identification of individuals at high risk. It is the goal of the molecular dosimetry field to provide facile and accurate biomarkers to identify people at high risk for carcinogen exposure and consequent adverse health effects. We have developed methods to defect the major aflatoxin DNA adduct, aflatoxin N7-guanine (AFB-N7-guanine), in urine, examined the dose-response characteristics in people living in China and The Gambia, and have found an excellent association of this biomarker with exposure. In addition to exposure studies in people, our laboratories have monitored AFB-N7-guanine excretion in the urine of rats whose risk for developing cancer has been modulated with dietary chemoprotective agents such that independent groups of animals receiving the same dosage of aflatoxin B1 were at either high or low risk for tumorigenesis. The production of DNA damage by aflatoxins is not the exclusive mechanism for liver cancer. Many other factors, including hepatitis B virus, cell proliferation, and nutritional status, can exert strong modification effects in human disease. Thus, molecular epidemiological investigations that examine only one biomarker may greatly underestimate or overestimate the risk for an individual.(ABSTRACT TRUNCATED AT 250 WORDS)
Groopman
J D
JD
Department of Environmental Health Sciences, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD 21205.
Wild
C P
CP
Hasler
J
J
Junshi
C
C
Wogan
G N
GN
Kensler
T W
TW
D000293:Adolescent; D000328:Adult; D016604:Aflatoxin B1 / Q000652:urine; D000348:Aflatoxins / Q000008:administration & dosage / Q000009:adverse effects* / Q000652:urine; D000818:Animals; D015415:Biomarkers / Q000652:urine; D002681:China; D004247:DNA / Q000652:urine; D018736:DNA Adducts; D004249:DNA Damage; D005260:Female; D005714:Gambia; D006147:Guanine / Q000652:urine*; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000652:urine; D008297:Male; D008875:Middle Aged; D051381:Rats; D011916:Rats, Inbred F344
D000348:Aflatoxins; D015415:Biomarkers; D018736:DNA Adducts; C072611:aflatoxin B1-DNA adduct; D006147:Guanine; D004247:DNA; D016604:Aflatoxin B1