Oesch F, Aulmann W, Platt K L, Doerjer G
Arch Toxicol Suppl. 1987;10:172-9. doi: 10.1007/978-3-642-71617-1_16.
After metabolic activation of benzo[a]pyrene to the 7,8-dihydrodiol-9,10-epoxide, this ultimate carcinogen preferentially binds to the exocyclic amino group of guanine. In order to investigate possible interindividual differences in the capacity of repair of the DNA adducts formed from benzo[a]pyrene 7,8-dihydrodiol 9,10-epoxide, their persistence in freshly isolated lymphocytes of several donors was studied. The results show a surprisingly large interindividual variation in DNA adduct formation and their persistence in freshly isolated lymphocytes. This range included several individuals with an apparent complete lack of repair capability for these adducts. Compared with controls, smokers showed on average a lower initial extent of the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide, suggesting induction of inactivating enzymes. However, one of the smokers was an individual with apparent complete lack of repair for the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide, combining exposure to benzo[a]pyrene with a long persistence of the DNA adducts formed from benzo[a]pyrene-7,8-dihydrodiol 9,10-epoxide. The investigation of the DNA repair of methylnitrosourea-induced lesions showed significant interindividual differences in the adaptive response triggered by repeated exposure to the carcinogen, whereas the interindividual variations after single doses were low.
苯并[a]芘代谢活化为7,8 - 二氢二醇 - 9,10 - 环氧化物后，这种最终致癌物优先与鸟嘌呤的外环氨基结合。为了研究由苯并[a]芘7,8 - 二氢二醇9,10 - 环氧化物形成的DNA加合物修复能力的个体差异，对几名供体新鲜分离的淋巴细胞中这些加合物的持久性进行了研究。结果显示，DNA加合物的形成及其在新鲜分离淋巴细胞中的持久性存在惊人的个体差异。这个范围包括几个明显完全缺乏修复这些加合物能力的个体。与对照组相比，吸烟者由苯并[a]芘 - 7,8 - 二氢二醇9,10 - 环氧化物形成的DNA加合物的初始程度平均较低，这表明诱导了失活酶。然而，其中一名吸烟者明显完全缺乏对由苯并[a]芘 - 7,8 - 二氢二醇9,10 - 环氧化物形成的DNA加合物的修复能力，将苯并[a]芘暴露与由苯并[a]芘 - 7,8 - 二氢二醇9,10 - 环氧化物形成的DNA加合物的长期持久性结合在一起。对甲基亚硝基脲诱导损伤的DNA修复研究表明，重复接触致癌物引发的适应性反应存在显著的个体差异，而单次剂量后的个体差异较小。
