Langenbach R, Rudo K
Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709.
Cell Biol Toxicol. 1988 Dec;4(4):453-65. doi: 10.1007/BF00117773.
The metabolism and mutagenic activation of 2-acetylaminofluorene by human and rat hepatocytes and kidney cells were measured. High performance liquid chromatography was used to separate the 2-acetylaminofluorene metabolites, and a cell-mediated Salmonella typhimurium mutagenesis assay was used to detect mutagenic intermediates. Rat and human differences were observed with cells from both organs and levels of metabolism and mutagenesis were higher in human cells. Within a species, liver and kidney cell differences were also evident, with levels of hepatocyte-mediated metabolism and mutagenesis being greater than kidney cells. Human inter-individual variation was apparent with cells from both organs, but the variation observed was significantly greater in hepatocytes than kidney cells. A knowledge of such differences, including an understanding that they may vary with the chemical being studied, should be useful in the extrapolation of rodent carcinogenesis data to humans.
对人和大鼠的肝细胞及肾细胞中2-乙酰氨基芴的代谢及诱变活化进行了测定。采用高效液相色谱法分离2-乙酰氨基芴代谢物，并采用细胞介导的鼠伤寒沙门氏菌诱变试验检测诱变中间体。在两个器官的细胞中均观察到大鼠和人类的差异，且人类细胞中的代谢和诱变水平更高。在一个物种内，肝细胞和肾细胞的差异也很明显，肝细胞介导的代谢和诱变水平高于肾细胞。两个器官的细胞均显示出人类个体间的差异，但观察到的差异在肝细胞中比在肾细胞中显著更大。了解这些差异，包括认识到它们可能因所研究的化学物质而异，对于将啮齿动物致癌数据外推至人类应是有用的。
