Niwa T, Yamazoe Y, Kato R
Mutat Res. 1982 Aug;95(2-3):159-70. doi: 10.1016/0027-5107(82)90254-8.
Microsomal activation was required for the expression of the mutagenicity of 2-amino-9H-pyrido[2,3-b]indole (A alpha C) toward Salmonella typhimurium TA98. Pretreatment of rats with PCB, 3-methylcholanthrene or phenobarbital increased the mutagenic activating ability of hepatic microsomes by 16-, 10- and 2-fold, respectively, as compared with the untreated. The mutagenic activation of A alpha C by microsomes from PCB-treated rats was inhibited by ellipticine and alpha-naphthoflavone, whereas SKF 525-A and metyrapone showed a slight or no inhibitory effect, indicating that the P-448 form of cytochrome P-450 is involved in the mutagenic activation of A alpha C. Metabolic activation of A alpha C was studied by a high-performance liquid chromatography and Salmonella/microsome assay system, and the mutagenic metabolites formed were determined to be the N-hydroxy and nitroso derivatives, from the results of reaction with oxidizing or reducing agents. These results strongly indicate that N-hydroxylation of A alpha C by the P-448 type of cytochrome P-450 is essential for the mutagenic activation.
2-氨基-9H-吡啶并[2,3-b]吲哚（AαC）对鼠伤寒沙门氏菌TA98的致突变性表达需要微粒体激活。与未处理的大鼠相比，用多氯联苯（PCB）、3-甲基胆蒽或苯巴比妥预处理大鼠后，肝微粒体的诱变激活能力分别提高了16倍、10倍和2倍。椭圆玫瑰树碱和α-萘黄酮可抑制PCB处理大鼠微粒体对AαC的诱变激活，而SKF 525-A和甲吡酮的抑制作用轻微或无抑制作用，这表明细胞色素P-450的P-448形式参与了AαC的诱变激活。通过高效液相色谱和沙门氏菌/微粒体分析系统研究了AαC的代谢激活，并根据与氧化剂或还原剂反应的结果确定形成的诱变代谢产物为N-羟基和亚硝基衍生物。这些结果有力地表明，细胞色素P-450的P-448类型对AαC的N-羟基化对于诱变激活至关重要。
