Kugler U, Bauchinger M, Schmid E, Göggelmann W
Mutat Res. 1987 Mar;187(3):151-6. doi: 10.1016/0165-1218(87)90082-6.
Comparative results are presented on the effectiveness of rat-liver S9 or microsomal mix (M mix) in activating cyclophosphamide (CP) and its ability to induce a clastogenic effect in human lymphocytes in vitro. Structural chromosome changes were analysed exclusively in 1st division (M1) metaphases post-exposure. A high genotoxic response was observed for both metabolizing systems used. With an exposure of 2 h to different concentrations of S9 or M mix, the highest aberration yields were always found for the highest protein content. For CP treatment times of 1, 2 or 4 h together with S9 mix (protein content 10 mg/ml) or M mix (4 mg/ml), the latter was more efficient. With both systems, a lower clastogenic effect of CP was found at 4 h exposure than at 1 h or 2 h. Only a weak cytotoxic effect, reflected mainly by the reduction in the percentage of 3rd cycle cells (M3), and measured in terms of the proportion of M1, M2 and M3 cells, was induced by both systems.
本文给出了大鼠肝脏S9或微粒体混合物(M混合物)在体外激活环磷酰胺(CP)的有效性及其诱导人淋巴细胞产生致断裂效应能力的比较结果。仅在暴露后的第1次分裂(M1)中期分析结构染色体变化。对于所使用的两种代谢系统,均观察到高遗传毒性反应。在暴露于不同浓度的S9或M混合物2小时的情况下,蛋白质含量最高时总是出现最高的畸变率。对于与S9混合物(蛋白质含量10mg/ml)或M混合物(4mg/ml)一起处理1、2或4小时的CP,后者更有效。使用这两种系统时,暴露4小时的CP致断裂效应低于1小时或2小时。两种系统均仅诱导了微弱的细胞毒性效应,主要表现为第3周期细胞(M3)百分比的降低,并根据M1、M2和M3细胞的比例进行测定。