Neonatal diethylstilbestrol treatment alters aflatoxin B1-DNA adduct concentrations in adult rats.
Aflatoxin B1-DNA adduct concentrations were measured in the livers of adult Sprague-Dawley CD rats treated on days 2, 4, and 6 postnatally with 1.45 mumols of diethylstilbestrol and in adulthood with phenobarbital, 3-methylcholanthrene, or vehicle prior to treatment with aflatoxin B1. Aflatoxin B1 (1 mg/kg) was injected 5 hr prior to killing the rats. Female rats exposed neonatally to diethylstilbestrol had significantly higher aflatoxin B1-DNA adduct concentrations (three- to sixfold) than adult female rats treated neonatally with propylene glycol. Liver aflatoxin B1-DNA adduct concentrations were slightly higher in control males as compared to adduct concentrations in neonatally diethylstilbestrol-treated males, as compared to adduct concentrations in control females (not significant [NS]). Phenobarbital and 3-methylcholanthrene treatment followed by aflatoxin B1 injection resulted in decreased aflatoxin B1-DNA adduct concentrations in all rats. Our results demonstrate that neonatal exposure to diethylstilbestrol alters the capacity of adult female rats to form and/or dispose of carcinogen-DNA adducts following a single dose of aflatoxin B1 (increased adduct concentration). This alteration may be a consequence of altered imprinting mechanisms with diethylstilbestrol causing developmental modifications early in life. The animals were, however, able to respond to cytochrome P-450 and P-448 inducers as evidenced by decreased aflatoxin B1-DNA adduct concentrations.
Lamartiniere
C A
CA
Department of Environmental Health Sciences, University of Alabama, Birmingham 35294.
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D005260:Female; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D011743:Pyrimidines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013737:Testis / Q000033:anatomy & histology; D013997:Time Factors
D000348:Aflatoxins; D002273:Carcinogens; D011743:Pyrimidines; D008748:Methylcholanthrene; C061392:aflatoxin B1-formamidopyrimidine; D004054:Diethylstilbestrol; D004247:DNA; D016604:Aflatoxin B1; D010634:Phenobarbital