ORGAN AND SPECIES SPECIFICITIES OF CHEMICAL CARCINOGENS

人类和啮齿动物组织代谢已知物质的能力 疑似致癌物质正在调查中。新陈代谢 这些化学物质对人体组织的影响及其遗传毒性 然后将激活的结果与啮齿动物的结果进行比较 纸巾。人和啮齿动物肝肾细胞代谢的研究 模型致癌物，苯并(A)芘和乙酰氨基荧烯，有 已经研究过了。对于人类肝脏，9个单独的组织样本 已经进行了调查，并对乙酰氨基荧中的八个 9个人类样本比大鼠的代谢物更活跃 肝细胞。整个人类的个体间变异 新陈代谢大约是3倍，尽管个体差异很大。 代谢物高达35倍。人的能力 肝细胞将这些羟基产物与硫酸盐偶联 或葡萄糖醛酸的含量也高于大鼠肝细胞，并且 人类个体间对结合物的变异约为8倍。为 苯并(A)芘，人类总代谢率的差异 肝细胞和大鼠肝细胞较少。关于肾脏的研究 组织也表明，人类细胞比 大鼠肾细胞产生乙酰氨基荧代谢物； 这两个物种的肾细胞都没有肝细胞那么活跃。 同样，人类肾脏的个体间变异约为3倍 观察其代谢情况。同样是苯并(A)芘，差异 人和大鼠肾细胞之间的总代谢较少 而不是乙酰氨基荧烯。调查结果表明， 个体间差异的程度可能随化学物质的不同而不同 正在研究中。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物质的不同而变化。 类，了解这些物种的差异将是 在将啮齿动物致癌数据外推到 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.