Iwata H, Yoshimi N, Mori Y, Hara A, Mori H
Department of Pathology, Gifu University School of Medicine, Japan.
Mutat Res. 1990 May;244(1):1-6. doi: 10.1016/0165-7992(90)90099-6.
The genotoxicity of 4 heterocyclic amines, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 2-aminodipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2) was examined in the hepatocyte primary culture (HPC)/DNA-repair assay using hepatocytes of rats and mice pretreated with 3-methylcholanthrene (MC), and the results were compared with those obtained in a previous assay with hepatocytes of normal rodents. All of these heterocyclic amines clearly elicited positive responses of DNA repair in the assay with hepatocytes of the rodents given MC, although in the regular HPC/DNA-repair test without MC pretreatment Tyr-P-2 and Glu-P-2 were negative in rat hepatocytes, and Try-P-2 was also negative in mouse hepatocytes. The level of unscheduled DNA synthesis induced by these positive compounds in the assay with hepatocytes of MC-treated rodents was much higher than that in the assay with hepatocytes of normal rodents. These results are basically in agreement with the reports that this class of compounds is highly activated metabolically by the cytochrome P-450 system from liver microsomes.
使用经3-甲基胆蒽（MC）预处理的大鼠和小鼠的肝细胞，在肝细胞原代培养（HPC）/DNA修复试验中检测了4种杂环胺，即3-氨基-1,4-二甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-1）、3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚（Trp-P-2）、2-氨基-6-甲基二吡啶并[1,2-a:3',2'-d]咪唑（Glu-P-1）和2-氨基二吡啶并[1,2-a:3',2'-d]咪唑（Glu-P-2）的遗传毒性，并将结果与先前用正常啮齿动物肝细胞进行的试验结果进行比较。在给予MC的啮齿动物肝细胞试验中，所有这些杂环胺均明显引发了DNA修复的阳性反应，尽管在未经MC预处理的常规HPC/DNA修复试验中，Tyr-P-2和Glu-P-2在大鼠肝细胞中呈阴性，Try-P-2在小鼠肝细胞中也呈阴性。在经MC处理的啮齿动物肝细胞试验中，这些阳性化合物诱导的非定标DNA合成水平远高于正常啮齿动物肝细胞试验中的水平。这些结果基本上与这类化合物在肝微粒体细胞色素P-450系统中被高度代谢激活的报道一致。
