DiGiovanni J, Nebzydoski A P, Decina P C
Cancer Res. 1983 Sep;43(9):4221-6.
The formation of DNA adducts from [3H]-7-hydroxymethyl-12-methylbenz(a)anthracene (7-OHM-12-MBA) and [3H]-7,12-dimethylbenz(a)anthracene (DMBA) in the epidermis of Sencar mice was analyzed. Comparison of Sephadex LH-20 chromatographic profiles of DNA samples isolated from mice treated with DMBA or 7-OHM-12-MBA suggested that the DMBA-treated animals contained DNA adduct(s) derived from the further metabolism of 7-OHM-12-MBA. Further analysis of DNA samples from DMBA-treated mice by high-pressure liquid chromatography demonstrated the presence of 5 DNA adducts which were chromatographically indistinguishable from the DNA adducts formed in 7-OHM-12-MBA-treated mice. Epidermal homogenates were utilized to catalyze the covalent binding of [3H]DMBA and [3H]-7-OHM-12-MBA to calf thymus DNA in vitro. Under conditions of limiting concentrations of [3H]DMBA, the majority of the DNA adducts formed chromatographed in regions where 7-OHM-12-MBA-DNA adducts eluted. A major DMBA-DNA adduct formed in this in vitro system eluted with the same retention time as did the major 7-OHM-12-MBA-DNA adduct formed in mouse skin in vivo. These results when coupled with the in vivo data suggest that 7-OHM-12-MBA is an intermediate for at least some of the binding of DMBA to epidermal DNA in Sencar mice.
分析了在Sencar小鼠表皮中由[3H]-7-羟甲基-12-甲基苯并(a)蒽（7-OHM-12-MBA）和[3H]-7,12-二甲基苯并(a)蒽（DMBA）形成的DNA加合物。对用DMBA或7-OHM-12-MBA处理的小鼠分离的DNA样品进行Sephadex LH-20色谱分析表明，用DMBA处理的动物含有源自7-OHM-12-MBA进一步代谢的DNA加合物。通过高压液相色谱对用DMBA处理的小鼠的DNA样品进行进一步分析，结果表明存在5种DNA加合物，其色谱行为与用7-OHM-12-MBA处理的小鼠中形成的DNA加合物无法区分。利用表皮匀浆在体外催化[3H]DMBA和[3H]-7-OHM-12-MBA与小牛胸腺DNA的共价结合。在[3H]DMBA浓度有限的条件下，形成的大多数DNA加合物在7-OHM-12-MBA-DNA加合物洗脱的区域进行色谱分离。在该体外系统中形成的一种主要DMBA-DNA加合物的洗脱保留时间与在小鼠皮肤体内形成的主要7-OHM-12-MBA-DNA加合物相同。这些结果与体内数据相结合表明，7-OHM-12-MBA是DMBA与Sencar小鼠表皮DNA结合的至少某些过程的中间体。
