Selkirk J K, Croy R G, Wiebel F J, Gelboin H V
Cancer Res. 1976 Dec;36(12):4476-9.
Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with a reduction of the K-region metabolites and a marked increase in 9-hydroxybenzo(a)-pyrene. These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. These results suggest that activation and detoxification of benzo(a)pyrene may be species and tissue variable, and susceptibility and resistence to malignant transformation may be predicted on induction of a fortuitous combination of intermediate metabolic steps.
用叙利亚仓鼠和NIH瑞士小鼠的啮齿动物肝脏微粒体(斯普拉格-道利大鼠)及啮齿动物胚胎细胞已显示出苯并(a)芘代谢物模式的差异。经甲基胆蒽诱导的啮齿动物肝脏在不同物种间显示出明显的定量变化。在小鼠和仓鼠胚胎传代培养物中还发现了模式变化,即K区代谢物减少,9-羟基苯并(a)芘显著增加。这些结果表明细胞单加氧酶对致癌物的攻击具有区域特异性,这与微粒体酶对苯并(a)芘的肝脏攻击不同。这些结果表明,苯并(a)芘的激活和解毒可能因物种和组织而异,对恶性转化的易感性和抗性可根据中间代谢步骤的偶然组合诱导来预测。