Todorovic R, Ariese F, Devanesan P, Jankowiak R, Small G J, Rogan E, Cavalieri E
Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Chem Res Toxicol. 1997 Sep;10(9):941-7. doi: 10.1021/tx970003y.
Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable adducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the depurinating and stable DNA adducts of DMBA and identification of the depurinating adducts of BP formed in rat mammary glands in the 24 h after 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 were formed from the diol epoxide(s) of DMBA. Depurinating adducts of BP with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gua, were identified in rat mammary glands treated with BP. The major stable adduct, formed via the diol epoxide pathway, BP-diol epoxide-10-N2dG, accounted for over 64% of all the stable adducts. Three other BP-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical cations and stable adducts via the diol epoxides.
7,12-二甲基苯并[a]蒽（DMBA）和苯并[a]芘（BP）在大鼠乳腺中均具有致癌性。先前已对DMBA和BP在体外及小鼠皮肤中形成的脱嘌呤和稳定加合物进行了鉴定和定量。本文报道了DMBA脱嘌呤和稳定DNA加合物的鉴定以及定量，以及在乳腺内注射DMBA或BP后24小时大鼠乳腺中形成的BP脱嘌呤加合物的鉴定。DMBA的脱嘌呤加合物占所有检测到加合物的52%，是DMBA在12-甲基处与腺嘌呤（Ade）或鸟嘌呤（Gua）的N-7结合形成的，即7-甲基苯并[a]蒽（MBA）-12-CH2-N7Ade（39%）和7-MBA-12-CH2-N7Gua（13%）。所有稳定加合物均由DMBA的二醇环氧化物形成。在用BP处理的大鼠乳腺中鉴定出了BP与鸟嘌呤的脱嘌呤加合物，即8-（BP-6-基）-鸟嘌呤（BP-6-C8Gua）和BP-6-N7Gua。通过二醇环氧化物途径形成的主要稳定加合物BP-二醇环氧化物-10-N2dG占所有稳定加合物的64%以上。另外三种BP-DNA稳定加合物仍未鉴定出来。因此，大鼠乳腺细胞主要通过其自由基阳离子形成DMBA和BP的脱嘌呤加合物，并通过二醇环氧化物形成稳定加合物。
