Robbiano L, Mereto E, Corbu C, Brambilla G
Institute of Pharmacology, University of Genoa, Italy.
Mutat Res. 1996 May;368(1):41-7. doi: 10.1016/s0165-1218(96)90038-5.
Seven N-nitroso compounds (NOC), known to induce kidney tumors in rats, were assayed for DNA-damaging activity in primary cultures of human and rat kidney cells. DNA fragmentation was measured by the alkaline elution technique. Positive responses were obtained in cells of both species with N-nitrosodimethylamine (32 mM), N-nitrosodiethylamine (32 mM), N-nitrosodi-n-propylamine (10 mM), N-ethyl-N-hydroxyethylnitrosamine (18 mM), and streptozotocin (1 mM). N-nitrosodiethanolamine and N-nitrosomorpholine were inactive at the highest concentration tested (32 mM). The responses of human kidney cells were qualitatively similar to those of rat kidney cells, but statistically significant differences between the two species in the DNA-damaging potencies were observed with N-ethyl-N-hydroxyethylnitrosamine and streptozotocin, both more genotoxic in rat cells. Taken as a whole, the results suggest on the one hand that the five active NOC might be carcinogenic for the kidney in humans, and on the other hand that the rat kidney cell/DNA damage assay is a valid model for predicting the genotoxic potential of NOC in human kidney cells.
已知七种可在大鼠体内诱发肾肿瘤的N-亚硝基化合物（NOC），在原代培养的人肾细胞和大鼠肾细胞中进行了DNA损伤活性检测。通过碱性洗脱技术测量DNA片段化。在用N-亚硝基二甲胺（32 mM）、N-亚硝基二乙胺（32 mM）、N-亚硝基二正丙胺（10 mM）、N-乙基-N-羟乙基亚硝胺（18 mM）和链脲佐菌素（1 mM）处理时，两种细胞均获得阳性反应。N-亚硝基二乙醇胺和N-亚硝基吗啉在测试的最高浓度（32 mM）下无活性。人肾细胞的反应在性质上与大鼠肾细胞相似，但在用N-乙基-N-羟乙基亚硝胺和链脲佐菌素处理时，观察到两种细胞在DNA损伤效力上存在统计学显著差异，二者在大鼠细胞中的遗传毒性更强。总体而言，结果一方面表明这五种活性NOC可能对人类肾脏具有致癌性，另一方面表明大鼠肾细胞/DNA损伤检测是预测NOC在人肾细胞中遗传毒性潜力的有效模型。
