Degawa M, Arai H, Kubota M, Hashimoto Y
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Biol Pharm Bull. 1995 Sep;18(9):1215-8. doi: 10.1248/bpb.18.1215.
Male F344 rats were pretreated with lead nitrate, nickel chloride, cobalt chloride or cadmium chloride, and their effects on the induction of cytochrome P450 (CYP) enzymes, mainly CYP1A2 enzyme, with 2-methoxy-4-aminoazobenzene (2-MeO-AAB) in the livers were comparatively examined by enzymatical, immunochemical, and molecular biological methods. When rats were pretreated with each ionic metal, the total CYP amount in the liver microsomes decreased, as compared with that of rats treated with 2-MeO-AAB alone. However, among the ionic metals used only lead reduced the levels of the mRNA and protein of CYP1A2 induced with 2-MeO-AAB in the rat liver, and decreased the microsomal activity (per CYP) for CYP1A2-mediated mutagenesis. Furthermore, ionic lead, but not other ionic metals, showed an ability to induce a placental form of glutathione S-transferase (GST-P). The level of CYP1A2 induced with 2-MeO-AAB was decreased along with increase in that of the induced GST-P.
雄性F344大鼠用硝酸铅、氯化镍、氯化钴或氯化镉进行预处理，通过酶学、免疫化学和分子生物学方法比较研究了它们对肝脏中细胞色素P450（CYP）酶（主要是CYP1A2酶）诱导的影响，诱导剂为2-甲氧基-4-氨基偶氮苯（2-MeO-AAB）。当用每种离子金属对大鼠进行预处理时，与仅用2-MeO-AAB处理的大鼠相比，肝微粒体中的总CYP量减少。然而，在所使用的离子金属中，只有铅降低了大鼠肝脏中由2-MeO-AAB诱导的CYP1A2的mRNA和蛋白质水平，并降低了CYP1A2介导的诱变的微粒体活性（每CYP）。此外，离子铅而非其他离子金属表现出诱导胎盘型谷胱甘肽S-转移酶（GST-P）的能力。随着诱导的GST-P水平的增加，由2-MeO-AAB诱导的CYP1A2水平降低。
