The effect of CYP1A1 induction on the formation of benzo[a]pyrene adducts in liver and lung DNA and plasma albumin in rats exposed to benzo[a]pyrene:adduct quantitation by immunoassay and an HPLC method

Induction of cytochrome P450 enzymes by exposure to polycyclic aromatic hyd rocarbons (PAH) can result in both decreased or increased PAH adduct levels . The lung is a main target site for PAM-carcinogenesis. By HPLC determinat ion of B[a]P-r-7, t-8-dihydrodiol, t-9,10-epoxide (BPDE-I)-DNA. adducts in rat, the level of the ultimate carcinogenic B[a]P-metabolite was higher in lungs than in liver. However, measured by immunoassay, the total benzo[a]py rene (B[a]P)-DNA adduct levels were higher in liver than in lungs. Inductio n of CYP1A1 in vivo in rat by repeated i.p. doses of methylcholanthrene (MC ) prior to a single dose of B[a]P resulted in a 2.4 times increase in CYP1A 1 activity in liver tissue and 1.5 times higher levels of total B[a]P-DNA a dducts in lung and liver compared with controls which only received B[a]P. Increased levels of BPDE-I-DNA adducts were significantly correlated to inc reased CYP1A1 activity in induced lung tissue but not in liver. The times t o reach maximum adduct levers were similar for both controls and MC-induced rats in both lung and liver, and plasma albumin. The BPDE-I-albumin adduct s reached a maximum level around 1 day after B[a]P exposure and could not b e used as a reliable marker of the short term PAH exposure in this study.