Dose-dependent benzo(a)pyrene [B(a)P]–DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P

Abstract

In order to investigate the relationship between BaP–DNA adduct formation and long-term exposure to benzo(a)pyrene (BaP), DNA adduct levels in liver and lung tissues of male and female F-344 rats subchronically exposed to BaP were determined. Doses of 0, 5, 50, and 100 mg/kg BaP, representing control, low, intermediate, and high doses, respectively, were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver and lung tissues were removed, DNA was isolated and analyzed for BaP-induced DNA adducts by the 32P-postlabeling method using a four-directional thin-layer chromatography system. At low and intermediate BaP doses, DNA adduct levels in the tissues were significantly correlated with exposure. However, at high BaP doses, the dose-DNA adduct relationship became non-linear. Similarly, the relative DNA adducts persistence at intermediate and high doses were significantly higher than that measured at low dose. The low and intermediate dose linearity and high dose non-linearity may be due to saturation of metabolic activation and detoxification enzymes, and DNA repair processes.