Ayrton A D, McFarlane M, Walker R, Neville S, Coombs M M, Ioannides C
Department of Biochemistry, University of Surrey, Guildford, U.K.
Toxicology. 1990 Jan-Feb;60(1-2):173-86. doi: 10.1016/0300-483x(90)90171-c.
The hypothesis has been put forward that mutagenic polycyclic aromatic hydrocarbons which induce the P-450 I family of cytochromes, the major enzyme system responsible for their activation, are likely to be carcinogenic. In order to test this hypothesis, rats have been pretreated with a number of polycyclic aromatic hydrocarbons of different mutagenic and carcinogenic potency and hepatic P-450 I activity was monitored using chemical probes such as the O-deethylation of ethoxyresorufin and metabolic activation of Glu-P-1 to mutagens, and immunologically employing polyclonal antibodies against purified rat P-450 I A1. All compounds studied enhanced P-450 I activity and induced P-450 I apoproteins but the extent of induction was very markedly different. The results are discussed with reference to the mutagenicity of these chemicals in the Ames test and their carcinogenicity in the classical mouse skin model. A relationship appears to exist between carcinogenicity of polycyclic aromatic hydrocarbons and their ability to induce hepatic P-450 I activity.
诱导致细胞色素P - 450 I族（负责其激活的主要酶系统）的诱变多环芳烃可能具有致癌性。为了验证这一假说，用多种具有不同诱变和致癌效力的多环芳烃对大鼠进行预处理，并使用化学探针（如乙氧试卤灵的O - 去乙基化和将Glu - P - 1代谢激活为诱变剂）以及采用针对纯化的大鼠P - 450 I A1的多克隆抗体进行免疫监测肝P - 450 I活性。所有研究的化合物均增强了P - 450 I活性并诱导了P - 450 I载脂蛋白，但诱导程度差异非常显著。结合这些化学物质在艾姆斯试验中的诱变性及其在经典小鼠皮肤模型中的致癌性对结果进行了讨论。多环芳烃的致癌性与其诱导肝P - 450 I活性的能力之间似乎存在关联。
