Degawa M
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Yakugaku Zasshi. 1995 Jan;115(1):1-14. doi: 10.1248/yakushi1947.115.1_1.
The N-hydroxyl and/or N-acetoxy derivatives of carcinogenic 4-aminoazo dyes, which were thought to be proximate and ultimate metabolites, were synthesized in our laboratory in 1975, and their chemical and biological characteristics were further examined. The results strongly supported the hypothesis that the metabolic conversions, N-hydroxylation and its O-acylation, of carcinogenic aromatic amines are important processes for their carcinogenicity. Carcinogenic aromatic amines such as heterocyclic aromatic amines and aminoazo dyes induced predominantly cytochrome P450IA2 (CYP1A2), which is responsible for the mutagenic activation and N-hydroxylation of the amines in the rodent. The induction rate and total activity of this enzyme were well correlated with sex, species, and target organ differences in hepatocarcinogenic susceptibility of animals to the aromatic amines. During hepatocarcinogenic process with an aromatic amine, the expression and induction of CYP1A2 decreased especially in preneoplastic liver cells as judged by the expression of a placental form of glutathione S-transferase.
致癌性4-氨基偶氮染料的N-羟基和/或N-乙酰氧基衍生物被认为是近端和最终代谢产物，1975年在我们实验室合成，并进一步研究了它们的化学和生物学特性。结果有力地支持了以下假说：致癌性芳香胺的代谢转化，即N-羟基化及其O-酰化，是其致癌性的重要过程。致癌性芳香胺，如杂环芳香胺和氨基偶氮染料，主要诱导细胞色素P450IA2（CYP1A2），该酶负责啮齿动物体内胺的诱变激活和N-羟基化。该酶的诱导率和总活性与动物对芳香胺的肝癌致癌易感性中的性别、物种和靶器官差异密切相关。在用芳香胺进行肝癌致癌过程中，通过胎盘形式的谷胱甘肽S-转移酶的表达判断，CYP1A2的表达和诱导尤其在癌前肝细胞中降低。
