Pigott M, Dipple A
BRI-Basic Research Program, NCI-Frederick Cancer Research Facility, MD 21701.
Cancer Lett. 1988 Jun 30;40(3):291-7. doi: 10.1016/0304-3835(88)90088-2.
Female NIH Swiss mice were treated topically with either 0.01 or 0.1 mumol 7,12-[3H]dimethylbenz[a]anthracene and DNA was isolated either from the whole skin, the dermis or the epidermis. Levels of binding to DNA and levels of individual adducts formed were similar in all 3 tissue fractions for a given dose of carcinogen with levels for the epidermis being marginally greater than in the other fractions. In all tissue fractions, the syn dihydrodiol epoxide-deoxyribonucleoside adducts were responsible for a greater fraction of total binding at the higher, than at the lower, carcinogen dose. The mechanism of metabolic activation of 7,12-dimethylbenz[a]anthracene for DNA binding is, therefore, qualitatively the same in both the dermis and epidermis. Quantification of adducts suggests some subtle differences between the DMBA activating systems in dermis and epidermis.
雌性NIH瑞士小鼠分别用0.01或0.1微摩尔的7,12-[³H]二甲基苯并[a]蒽进行局部处理,然后从全皮、真皮或表皮中分离DNA。对于给定剂量的致癌物,在所有3种组织组分中,与DNA的结合水平和形成的单个加合物水平相似,表皮中的水平略高于其他组分。在所有组织组分中,在较高致癌物剂量下,反式二氢二醇环氧化物 - 脱氧核糖核苷加合物在总结合中所占的比例高于较低剂量时。因此,7,12 - 二甲基苯并[a]蒽代谢激活以进行DNA结合的机制在真皮和表皮中在定性上是相同的。加合物的定量表明真皮和表皮中的DMBA激活系统之间存在一些细微差异。