ORGAN AND SPECIES DIFFERENCES IN CHEMICAL CARCINOGENS

新陈代谢人类和啮齿动物组织代谢已知或怀疑的能力 正在对化学致癌物质进行调查。新陈代谢谱和 具有人体组织激活作用的化学物质的遗传毒性 与啮齿动物组织的结果进行比较。人和啮齿动物肝脏 和肾脏细胞代谢的模型致癌物苯并(A)芘和 对乙酰氨基荧烯进行了研究。对于人类肝脏，9个个体 已经对组织样本进行了调查，发现有8个组织样本是乙酰氨基荧烯 在九个人类样本中，比老鼠更活跃的代谢物 肝细胞。整个人类的个体间变异 新陈代谢大约是原来的3倍，尽管个体代谢物不同 高达35倍。人肝细胞的结合能力 这些与硫酸盐或葡萄糖醛酸羟化的产物也是 大于大鼠肝细胞和人类个体间差异 结合率约为8倍。对于苯并(A)芘， 人肝细胞与大鼠肝细胞之间的总代谢较少。 对肾脏组织的研究也表明，人类细胞 比大鼠肾细胞更能产生乙酰氨基荧烯 代谢物；但两个物种的肾脏细胞的活性都低于 肝细胞。再说一次，人类的个体间变异是3倍 观察肾脏代谢情况。同样是苯并(A)芘，差异 在人与啮齿动物之间的总代谢中 大鼠肾细胞数少于乙酰氨基荧组。调查结果 表明个体间差异的程度可能随 正在研究的化学物质。此外，人类和啮齿动物之间的差异 化学致癌物的新陈代谢也会随着化学类别的不同而变化， 而了解这些物种的差异将是必要的 啮齿动物致癌数据外推到人类。

The ability of human and rodent tissues to metabolize known or suspected chemical carcinogens is being investigated. The metabolic profiles and genetic toxicities of the chemicals with human tissue activation are then being compared to the results from rodent tissues. Human and rodent liver and kidney cell metabolism of the model carcinogens, benzo (a) pyrene and acetylaminofluorene, have been studied. For human liver, nine individual tissue specimens have been investigated and for acetylaminofluorene eight of the nine human samples were more active metabolizers than the rat hepatocytes. The interindividual variation in the overall human metabolism was about 3-fold, although variation in individual metabolites was as high as 35-fold. The ability of human hepatocytes to conjugate these hydroxylated products with sulfate or glucuronic acid was also greater than in rat hepatocytes and the human interindividual variation to conjugate was about 8-fold. For benzo(a) pyrene, the differences in total metabolism between human hepatocytes and rat hepatocytes were less. Studies with kidney tissues have also indicated that human cells are more active than rat kidney cells in producing acetylaminofluorene metabolites; but kidney cells from both species are less active than hepatocytes. Again, about a 3-fold interindividual variation in human kidney metabolism was observed. Again with benzo(a) pyrene, differences in total metabolism between human and rodent metabolism between human and rat kidney cells were less than for acetylaminofluorene. The findings indicate that the extent of interindividual variations can vary with the chemical being studied. Furthermore, differences between human and rodent metabolism of chemical carcinogens can also vary with the chemical class, and understanding these species differences will be necessary in the extrapolation of rodent carcinogenesis data to humans.