DETERMINATION OF BENZO[A]PYRENE-DNA AND 7,12-DIMETHYLBENZ[A]ANTHRACENE-DNA ADDUCTS FORMED IN RAT MAMMARY-GLANDS

Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable ad ducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the de purinating and stable DNA adducts of DMBA and identification of the de purinating adducts of BP formed in rat mammary glands in the 24 h afte r intramammillary injection of DMBA or BP are reported in this paper. The depurinating adducts of DMBA, which constitute 52% of all adducts detected, are DMBA bound at the 12-methyl group to the N-7 of adenine (Ade) or guanine (Gua), namely, 7-methylbenz[a]anthracene (MBA)-12-CH2 -N7Ade (39%) and 7-MBA-12-CH2-N7Gua (13%). All of the stable adducts w ere formed from the diol epoxide(s) of DMBA. Depurinating adducts of B P with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gu a, were identified in rat mammary glands treated with BP. The major st able adduct, formed via the diol epoxide pathway, BP-diol epoxide-10-N (2)dG, accounted for over 64% of all the stable adducts. Three other B P-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical c ations and stable adducts via the diol epoxides.