Abstract
Aflatoxin B~1~‐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 μmol of diethylstilbestrol and in adulthood with phenobarbital, 3‐methylchlanthrene, or vehicle prior to treatment with aflatoxin B~1~. Aflatoxin B~1~ (1 mg/kg) was injected 5 hr prior to killing the rats. Female rats exposed neonatally to diethylstilbestrol had significantly higher aflatoxin B~1~‐DNA adduct concentrations (three‐ to sixfold) than adult female rats treated neonatally with propylene glycol. Liver aflatoxin B~1~‐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 B~1~ injection resulted in decreased aflatoxin B~1~‐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 B~1~ (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 B~1~‐DNA adduct concentrations.