Formation of benzo[a]pyrene metabolite-nucleoside adducts in isolated perfused rat and mouse liver and in mouse lung slices

Abstract

The formation of benzo[a]pyrene metabolite-nucleoside adducts in perfused rat and mouse liver and in mouse lung slices was studied by Sephadex LH20 chromatography. In liver from β-naphthoflavone-pretreated rats, four different deoxyribonucleoside complexes were observed; these are tentatively attributed to DNA modification by the 7,8-diol-9, 10-epoxide(s), secondary metabolites of benzo[a]pyrene quinones, the 4,5-oxide, and secondary metabolites of benzo[a]pyrene phenols. The diol-epoxide-deoxyribonucleoside adduct was also detected in perfused liver and in lung slices from 3-methylcholanthrene-treated genetically responsive C57BL/6N mice, whereas no adducts were detectable in such samples from 3-methylcholan-threne-treated genetically nonresponsive DBA/2N mice. In perfused liver of phenobarbital-pretreated rats, the 4,5-oxide-deoxyribonucleoside adduct was present. These results suggest that some of the benzo[a]pyrene metabolite-nucleoside complexes generated by microsomes and deproteinized DNA in vitro also occur in the intact rodent liver and lung tissues. Furthermore, complexes with the diol-epoxide(s) were observed with RNA from perfused liver of β-naphthoflavone-treated, but not from untreated or phenobarbital-treated rats. Complexes between ribonucleoside(s) and the diol-epoxide(s) were also found in perfusedliver or lung slices from genetically responsive but not from genetically nonresponsive mice.