ORGAN AND SPECIES SPECIFICITIES OF CHEMICAL CARCINOGENS

人类和啮齿类动物组织的代谢能力 怀疑致癌物正在调查中。 代谢 化学品对人体组织的遗传毒性 然后将激活与啮齿动物的结果进行比较， 组织中 人类和啮齿类动物的肝和肾细胞代谢 模型致癌物苯并（a）芘和乙酰氨基芴， 本文研究了 对于人类肝脏，9个单独的组织样本 已经研究过，对于乙酰氨基芴， 九个人类样本的代谢比大鼠更活跃 肝细胞 整体人类的个体差异 代谢约为3倍，尽管个体差异 代谢物的含量高达35倍。 人类的能力 肝细胞将这些羟基化产物与硫酸盐结合 或葡萄糖醛酸也高于大鼠肝细胞， 人个体间对缀合物变异约为8倍。 为 苯并（a）芘，人体总代谢的差异， 肝细胞和大鼠肝细胞较少。 组织也表明，人体细胞比 大鼠肾细胞产生乙酰氨基芴代谢物;但 来自这两个物种的肾细胞比肝细胞活性低。 同样，在人类肾脏中， 观察代谢情况。 再次与苯并（a）芘，差异 在人和大鼠肾细胞之间的总代谢中， 乙酰氨基芴。 调查结果表明， 个体间变异的程度可能因化学物质的不同而不同。 被研究。 此外，人类和啮齿动物之间的差异 化学致癌物的代谢也可以随着化学物质的不同而变化。 类，并了解这些物种的差异将是 啮齿动物致癌作用数据外推到 人类

The ability-of human and rodent tissues to metabolize known suspected 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 metaboli 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 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 human.