Hukkelhoven M W, Vromans E, Vermorken A J, Bloemendal H
Anticancer Res. 1982 Jan-Apr;2(1-2):89-94.
The formation of the 7, 8-a and 9, 10-dihydrodiol metabolites of benzo(a)pyrene, which are believed to play a role in the chemical induction of tumors, was investigated in cultures of human and murine origin. It was found that cultures of mouse (strain C3Hz) epidermal and skin fibroblastic cells showed inducible benzo(a)pyrene metabolism towards dihydrodiol metabolites, after pre-incubation with benz(a)anthracene. This was consistent with the increased in vivo formation of dihydrodiol metabolites of benzo(a)pyrene after injection with 3-methylcholanthrene. In contrast, in human cell cultures the metabolism of benzo(a)pyrene to the dihydrodiol metabolites was not enhanced after pre-exposure to benz(a)anthracene. This was the case in low-passage skin fibroblasts, primary epidermal skin cells, and primary keratinocytes from hair follicles. Moreover, other inducers of microsomal oxygenases, such as phenobarbital and 3-methylcholanthrene, were also unable to increase benzo(a)pyrene metabolism towards the dihydrodiol compounds. In view of these results, obtained using in vitro human and murine model systems, we may conclude that human and murine skin cell culture systems respond differently to pre-treatment with inducers of microsomal monooxygenases with respect to the metabolism of benzo(a)pyrene to reactive dihydrodiol metabolites. The possible implications for the human in vivo situation are discussed.
在人和鼠源的培养物中研究了苯并(a)芘的7,8 - a和9,10 - 二氢二醇代谢产物的形成，据信这些代谢产物在肿瘤的化学诱导中起作用。发现小鼠（C3Hz品系）表皮和皮肤成纤维细胞培养物在与苯并(a)蒽预孵育后，显示出对苯并(a)芘向二氢二醇代谢产物的诱导性代谢。这与注射3 - 甲基胆蒽后苯并(a)芘的二氢二醇代谢产物在体内形成增加相一致。相反，在人细胞培养物中，预暴露于苯并(a)蒽后，苯并(a)芘向二氢二醇代谢产物的代谢并未增强。低传代皮肤成纤维细胞、原代表皮细胞和毛囊原代角质形成细胞均是如此。此外，微粒体加氧酶的其他诱导剂，如苯巴比妥和3 - 甲基胆蒽，也不能增加苯并(a)芘向二氢二醇化合物的代谢。鉴于使用体外人和鼠模型系统获得的这些结果，我们可以得出结论，就苯并(a)芘向反应性二氢二醇代谢产物的代谢而言，人和鼠皮肤细胞培养系统对微粒体单加氧酶诱导剂的预处理反应不同。讨论了其对人体体内情况的可能影响。
