Nucleoside adducts from the in vitro reaction of benzo[a]pyrene-7,8-dihydrodiol 9,10-oxide or benzo[a]pyrene 4,5-oxide with nucleic acids

Abstract

The covalent binding of the carcinogens benzo[a]pyrene-4,5-oxide and benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide isomer I and isomer II to nucleic acids in aqueous acetone solutions was investigated. Benzo[a]pyrene-4,5-oxide reacted preferentially with guanosine residues. Benzo[a]pyrene-7,8-dihydrodiol-9,10-oxide isomer I and isomer II reacted extensively with guanosine, adenosine and cytidine residues. Time course studies showed that the reactivity of isomer I or isomer II with homopolyribonucleotides followed the order poly(G) > poly(A) > poly(C). Alkaline or enzymatic hydrolysis of the modified nucleic acids and subsequent chromatography on Sephadex LH-20 columns yielded benzo[a]pyrene-nucleotide adducts. These were enzymatically converted to the corresponding nucleosides which were resolved into several distinct components by high pressure liquid chromatography [HPLC]. Evidence was obtained for the presence of multiple nucleoside adducts of guanosine, adenosine, cytidine, deoxyguanosine, deoxyadenosine and deoxycytidine. The HPLC profiles of adducts formed with isomer I were different from the corresponding profiles of adducts formed with isomer II. Structural aspects of these nucleoside adducts are discussed.