Covalent binding of benzo[a]pyrene to macromolecules in lung and liver of rats following intratracheal instillation.

Benzo[a]pyrene (BP) was administered intratracheally to male Sprague-Dawley rats at a dose of 25 micrograms/kg. Covalent binding of BP metabolites to DNA, RNA and protein in lung and liver was analyzed 6 h after administration. In both lung and liver, relative amounts bound based on mass of each macromolecule decreased in the order RNA greater than protein greater than DNA. For DNA and RNA, but not protein, binding in liver exceeded that in lung. Types of DNA adducts in lung and liver were analyzed using boronate chromatography followed by HPLC. Several adducts were formed between BP metabolites and DNA in lung, and the adduct present in greatest amounts was that formed between deoxyguanosine and (+)-anti-BP diol epoxide (BPDE:dGuo). Only 2 adducts were distinguishable in liver. BPDE:dGuo was detected, though the predominant adduct, as yet unidentified, did not contain cis-vicinal hydroxyl groups.