ORGAN AND SPECIES SPECIFICITIES OF CHEMICAL CARCINOGENS

新陈代谢人类和啮齿动物组织代谢已知或 疑似化学致癌物质正在调查中。这个 化学物质的代谢特征和遗传毒性 然后将人体组织的激活与结果进行比较 从啮齿动物组织中提取以帮助推断啮齿动物的作用 对人类的潜在影响。人和啮齿动物的肝脏和 致癌芳香烃模型肾细胞代谢的实验研究 胺，乙酰氨基荧烯，已经完成。对于人类来说 肝脏，对9个单独的组织样本进行了调查和 与ALL观察到的羟化产物的复杂图案 案子。同样的羟化产物也被观察到 大鼠肝细胞；然而，九个人类样本中有八个是 比大鼠肝细胞更活跃的代谢物。这个 人类整体新陈代谢的个体间差异是 大约4倍；尽管个体代谢物的差异是 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 也比大鼠肝细胞和人类个体间的 对结合物的变异约为8倍。人肝细胞 在产生代谢物方面也比大鼠肝细胞更活跃 对鼠伤寒沙门氏菌有致突变作用。研究对象： 肾脏组织也表明，人类细胞比 比大鼠肾脏组织活跃也表明人类细胞 比大鼠肾细胞更活跃地产生羟化产物 和致突变的乙酰氨基荧代谢物，但肾细胞 这两种细胞的活性都不如肝细胞。再一次，关于 人类肾脏代谢的4倍个体间差异是 观察到的。这些研究的结果现在正在扩展到 其他NTP化学品，以确定这些数据在 结合药效学和遗传毒性数据可以 帮助啮齿动物进行人类外推。

The ability of human and rodent tissues to metabolize known or suspected chemical carcinogens is being investigated. The metabolic profile and genetic toxicity of the chemicals with human tissue activation are then being compared to the results from rodent tissues to aid the extrapolation of effects in rodents to potential effects in humans. Human and rodent liver and kidney cell metabolism of the model carcinogenic aromatic amine, acetylaminofluorene, has been completed. For human liver, nine individual tissue specimens have been investigated and a complex pattern of hydroxylated products observed with all cases. The same hydroxylated products were also observed with rat hepatocytes; however eight of the nine human samples were more active metabolizers than the rat hepatocytes. The interindividual variation in the overall human metabolism was about 4-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. Human hepatocytes were also more active that rat hepatocytes in producing metabolites which were mutagenic to Salmonella typhimurium. Studies with kidney tissues have also indicated that human cells are more active than rat kidney tissues have also indicated that human cells are more active that rat kidney cells in producing hydroxylated and mutagenic acetylaminofluorene metabolites; but kidney cells from both species are less active than hepatocytes. Again, about a 4-fold interindividual variation in human kidney metabolism was observed. The results of these studies are now being extended to other NTP chemicals to determine if these data when used in combination with pharmacodynamic and genetic toxicity data can aid in rodent to human extrapolation.