从人胎肝中纯化的P-450HFLb的免疫化学特性及毒理学意义。

Immunochemical characterization and toxicological significance of P-450HFLb purified from human fetal livers.

作者信息

Kitada M, Kato T, Ohmori S, Kamataki T, Itahashi K, Guengerich F P, Rikihisa T, Kanakubo Y

机构信息

Hospital Pharmacy, Chiba University Hospital, Japan.

出版信息

Biochim Biophys Acta. 1992 Oct 27;1117(3):301-5.

PMID:1420280

Abstract

Immunochemical properties of P-450HFLb purified from human fetal livers were investigated. P-450HFLb cross-reacted with antibodies to rat P-4501A1 but not with antibodies to CYP2A6, CYP2C9, CYP3A7 (P-450HFLa) and rat CYP2B1. In addition, P-450HFLb also cross-reacted with both monospecific antibodies to rat CYP1A1 and CYP1A2. However, P-450HFLb was shown to be an immunochemically distinct form of cytochrome P-450 from P-450PA (human CYP1A2). Immunoblot analysis of human fetal livers with the antibodies to P-450HFLb showed that P-450HFLb was expressed in all fetal livers studied although there appeared to be individual differences in the amounts of P-450HFLb expressed in fetal livers. The formation of mutagens from IQ (but not from AFB1) in fetal liver homogenates was inhibited by the antibodies to P-450HFLb in a dose dependent manner. These results suggest that P-450HFLb may be a form of human cytochrome P-450 classified into CYP1 gene family, and that the cytochrome P-450 is, in part, responsible for the mutagenic activation of IQ in human fetal livers as well as CYP3A7 (P-450HFLa).

摘要

对从人胎肝中纯化的P-450HFLb的免疫化学特性进行了研究。P-450HFLb与抗大鼠P-4501A1抗体发生交叉反应，但与抗CYP2A6、CYP2C9、CYP3A7（P-450HFLa）和大鼠CYP2B1抗体不发生交叉反应。此外，P-450HFLb还与抗大鼠CYP1A1和CYP1A2的单特异性抗体都发生交叉反应。然而，P-450HFLb被证明是一种在免疫化学上与P-450PA（人CYP1A2）不同的细胞色素P-450形式。用抗P-450HFLb抗体对人胎肝进行免疫印迹分析表明，在所研究的所有胎肝中都表达了P-450HFLb，尽管胎肝中P-450HFLb的表达量似乎存在个体差异。胎肝匀浆中由IQ（而非AFB1）形成诱变剂的过程被抗P-450HFLb抗体以剂量依赖的方式抑制。这些结果表明，P-450HFLb可能是人类细胞色素P-450的一种形式，属于CYP1基因家族，并且这种细胞色素P-450在一定程度上与人胎肝中IQ以及CYP3A7（P-450HFLa）的诱变活化有关。