Horner S A, Fry J R, Clothier R H, Balls M
Xenobiotica. 1985 Aug-Sep;15(8-9):681-6. doi: 10.3109/00498258509047427.
The cytotoxicity to V79 Chinese hamster fibroblasts of cyclophosphamide (CPA) metabolites, generated by rat-liver S9 fractions, has been compared in two assay systems with different endpoints of toxicity, namely, reduction of cloning efficiency and inhibition of cell growth. The two assay systems were found to be equally sensitive in detecting the metabolism-mediated cytotoxicity of CPA and gave similar ID50 values. Further studies confirmed the cytochrome P-450 enzyme requirement for the bioactivation of CPA to cytotoxic metabolites. CPA activation was mediated by phenobarbitone-inducible forms of cytochrome P-450, but not by beta-naphthoflavone-inducible forms.
比较了大鼠肝脏S9组分产生的环磷酰胺（CPA）代谢物对V79中国仓鼠成纤维细胞的细胞毒性，采用了两种具有不同毒性终点的检测系统，即克隆效率降低和细胞生长抑制。发现这两种检测系统在检测CPA的代谢介导细胞毒性方面同样敏感，并给出了相似的ID50值。进一步的研究证实了细胞色素P - 450酶对CPA生物活化成细胞毒性代谢物的需求。CPA的活化是由苯巴比妥诱导型细胞色素P - 450介导的，而不是由β-萘黄酮诱导型介导的。
