Kasper P, Madle S, George E
Institute for Drugs, Federal Health Office, Berlin, FRG.
Mutagenesis. 1988 Nov;3(6):521-5. doi: 10.1093/mutage/3.6.521.
The continuous rat hepatoma cell line H4IIEC3/G- and rat hepatocyte primary cultures (hpc) were compared with regard to their capacity to metabolize structurally different promutagens. The sensitivities of both activation systems were evaluated by comparing the induction of SCE in H4IIEC3/G- cells themselves with that ih V79 cells co-cultured with hpc. Of the six chemicals tested, aflatoxin B1 (AFB1), cyclophosphamide, dimethylnitrosamine and nitrosomorpholine (NM) were shown to be inducers of SCE in H4IIEC3/G- cells as well as in V79 cells with hepatocyte activation. 7,12-Dimethylbenzanthracene gave positive responses in hpc/V79 co-cultures but not in H4IIEC3/G- cells whereas benzo[a]pyrene was negative in both systems. These results suggest that H4IIEC3/G- cells retain metabolic activities to convert different indirect mutagens into their active forms and clearly indicate the presence of liver specific cytochrome P-450-dependent mono-oxygenases. However, freshly isolated hepatocytes are more efficient in metabolizing the test compounds. Although hpc provide only external activation, the V79 cells system appears to be more sensitive for the detection of promutagens.
对连续传代的大鼠肝癌细胞系H4IIEC3/G-和大鼠肝细胞原代培养物（hpc）代谢结构不同的前诱变剂的能力进行了比较。通过比较H4IIEC3/G-细胞自身以及与hpc共培养的V79细胞中姐妹染色单体交换（SCE）的诱导情况，评估了这两种活化系统的敏感性。在所测试的六种化学物质中，黄曲霉毒素B1（AFB1）、环磷酰胺、二甲基亚硝胺和亚硝基吗啉（NM）在H4IIEC3/G-细胞以及经肝细胞活化的V79细胞中均显示为SCE诱导剂。7,12-二甲基苯并蒽在hpc/V79共培养物中呈阳性反应，但在H4IIEC3/G-细胞中无阳性反应，而苯并[a]芘在两种系统中均为阴性。这些结果表明，H4IIEC3/G-细胞保留了将不同间接诱变剂转化为其活性形式的代谢活性，并清楚地表明存在肝脏特异性细胞色素P-450依赖性单加氧酶。然而，新鲜分离的肝细胞在代谢测试化合物方面更有效。虽然hpc仅提供外部活化，但V79细胞系统似乎对前诱变剂的检测更敏感。
