Ayrton A D, McFarlane M, Walker R, Neville S, Ioannides C
Department of Biochemistry, University of Surrey, Guildford, UK.
Carcinogenesis. 1990 May;11(5):803-9. doi: 10.1093/carcin/11.5.803.
The hypothesis has been put forward that genotoxic aromatic amines which induce the P450 I family of haemoproteins, the major enzyme involved in their bioactivation, are more likely to be carcinogenic when compared to those chemicals that fail to do so. Induction of the hepatic P450 I family of proteins by carcinogenic aromatic amines and their non-carcinogenic isomers and analogues was investigated in the rat and correlated to their carcinogenic potential. The activity of the P450 I A1 protein was monitored by the O-deethylation of ethoxyresorufin and of the P450 I A2 by the activation of the premutagen Glu-P-1 to mutagenic intermediates in the Ames test. Results were always confirmed immunologically in Western blots employing antibodies to rat P450 I A1 which recognize both proteins of the P450 I family. With all groups of chemicals used in the present study, the members displaying carcinogenicity were always the more potent inducers, while the non-carcinogenic isomers or analogues displayed little or no induction. It appears that a relationship exists between the carcinogenicity of aromatic amines and their ability to induce hepatic P450 I activity.
与无法诱导血红素蛋白P450 I家族（参与其生物活化的主要酶）的化学物质相比，诱导该家族的基因毒性芳香胺更有可能具有致癌性。在大鼠中研究了致癌芳香胺及其非致癌异构体和类似物对肝脏P450 I家族蛋白的诱导作用，并将其与它们的致癌潜力相关联。通过乙氧芴香豆素的O-去乙基化监测P450 I A1蛋白的活性，通过在Ames试验中将前诱变剂Glu-P-1活化为诱变中间体来监测P450 I A2的活性。在使用针对大鼠P450 I A1的抗体进行的蛋白质印迹中，结果总是通过免疫方法得到证实，该抗体可识别P450 I家族的两种蛋白质。对于本研究中使用的所有化学物质组，显示致癌性的成员总是更强的诱导剂，而非致癌异构体或类似物则几乎没有诱导作用或根本没有诱导作用。看来芳香胺的致癌性与其诱导肝脏P450 I活性的能力之间存在关联。
