Corsi C, Paolini M, Galli A, Bronzetti G, Cantelli Forti G
Teratog Carcinog Mutagen. 1985;5(4):223-30. doi: 10.1002/tcm.1770050403.
The degree of conversion of cyclophosphamide (CP) into mutagenic intermediates was studied using mouse erythrocytes as the metabolic activation system. The amount of mutagenic intermediates produced was measured indirectly in terms of induced frequencies of mitotic recombination, mitotic gene conversion, and reverse mutation in the diploid D7 strain of Saccharomyces cerevisiae. In the absence of S9 microsomal fraction or erythrocytes, CP did not induce any genetic response. In the presence of erythrocytes, on the other hand, CP clearly induced increases in the three genetic endpoints. The responses, however, were lower than those observed with the S9 activation system. The activating principle seems to be the oxyhemoglobin. In fact, neither p-nitroanisole O-demethylase activity nor genotoxic responses performed with red-blood cells from uninduced and PB-induced mice indicate that (possible) water-soluble forms of cytochrome P-450 were responsible for the activation of CP by erythrocytes.
以小鼠红细胞作为代谢活化系统，研究了环磷酰胺（CP）转化为诱变中间体的程度。诱变中间体的生成量通过酿酒酵母二倍体D7菌株中有丝分裂重组、有丝分裂基因转换和回复突变的诱导频率间接测定。在没有S9微粒体组分或红细胞的情况下，CP不会诱导任何遗传反应。另一方面，在有红细胞存在时，CP明显诱导了三个遗传终点的增加。然而，这些反应低于用S9活化系统观察到的反应。活化原理似乎是氧合血红蛋白。事实上，无论是对硝基苯甲醚O-脱甲基酶活性，还是用未诱导和经苯巴比妥诱导的小鼠的红细胞进行的遗传毒性反应，都表明（可能的）细胞色素P-450水溶性形式不是红细胞激活CP的原因。
