Martelli A, Robbiano L, Ghia M, Giuliano L, Angelini G, Brambilla G
Cancer Lett. 1986 Jan;30(1):11-6. doi: 10.1016/0304-3835(86)90126-6.
The genotoxicity of cimetidine, a drug widely used in the treatment of peptic ulcer, was examined in human hepatocyte primary cultures. No induction of unscheduled DNA synthesis, as detected by autoradiography, or of DNA fragmentation, as measured by alkaline elution, was seen in metabolically competent human hepatocytes exposed for 20 h to cimetidine concentrations ranging from 0.33 to 9 mM. These findings, which are in contrast with the previously observed capability of cimetidine to induce DNA damage and repair in rat hepatocyte primary cultures, suggest that for some chemicals the rat hepatocyte model might be an inappropriate predictor of potential genotoxic effects in the analogous human cells.
西咪替丁是一种广泛用于治疗消化性溃疡的药物，其遗传毒性在人肝细胞原代培养物中进行了检测。通过放射自显影检测，在代谢功能正常的人肝细胞中，将其暴露于浓度范围为0.33至9 mM的西咪替丁20小时，未观察到非程序性DNA合成的诱导，通过碱性洗脱测量也未观察到DNA片段化。这些发现与之前观察到的西咪替丁在大鼠肝细胞原代培养物中诱导DNA损伤和修复的能力形成对比，表明对于某些化学物质，大鼠肝细胞模型可能不是类似人类细胞中潜在遗传毒性效应的合适预测指标。
