METABOLISM OF XENOBIOTICS TO MUTAGENS USING NON-HEPATIC ENZYME SYSTEMS

使用非肝酶系统将异生物质代谢为诱变剂

• 批准号: 3941479
• 负责人: E ZEIGER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3941479
• 关键词: Salmonella; benzopyrenes; biotransformation; carbopolycyclic compound; cyclic amine; diol; epoxides; liver metabolism; microsomes; mutagen testing; mutagens; nitrosamines; prostaglandin endoperoxide synthase; quinoline; seminal vesicles; unspecific monooxygenase

Prostaglandin H synthase (PGH) is an oxidative microsomal enzyme system separate from the cytochrome P450 system most often used for oxidative metabolism of xenobiotics. PGH derived from ram seminal vesicles has been used in the past to metabolize a number of polycyclic aromatic hydrocarbon bay-region epoxides and aromatic amines to mutagens for Salmonella typhimurium. It was recently shown that PGH can metabolize a number of aromatic amines of the carboline and azaimidaozoarene classes that are formed during the cooking of beef to DNA-binding intermediates. Four of these chemicals, Trp-P-1, Trp-P-2, IQ, and MeIQ, which are potent mutagens in the presence of rat liver S-9, were tested with PGH. Mutagenicity was not obtained at doses comparable to those used with S-9. All four chemicals were direct-acting mutagens at doses 1000x those used with S-9. At these higher doses, PGH slightly enhanced the direct mutagenicity of Trp-P-2, had no effect on Trp-P-1, and decreased the mutagenicities of IQ and MeIQ. The direct-acting and PGH- mediated mutagenicity were highly dependent on pH and buffer composition.

前列腺素H合酶（PGH）是一种氧化微粒体 酶系统与细胞色素P450系统分离最多 通常用于异生物质的氧化代谢。 PGH衍生 在过去被用来代谢 许多多环芳烃海湾区环氧化物 和芳香胺对鼠伤寒沙门氏菌的诱变剂。 它 最近显示PGH可以代谢许多 咔啉和氮杂咪唑并唑芳烃类的芳族胺 在烹饪牛肉的过程中形成， 中间体的 其中四种化学物质Trp-P-1 Trp-P-2 IQ 和MeIQ，在大鼠肝脏存在下为强效诱变剂 S-9，用PGH检测。 未获得致突变性， 剂量与S-9使用的剂量相当。 这四种化学物质 剂量为S-9剂量的1000倍的直接作用诱变剂。 在 在这些较高剂量下，PGH略微增强了直接致突变性 对Trp-P-1没有影响，但降低了Trp-P-2的表达。 IQ和MeIQ的致突变性。 直接作用和PGH- 介导的致突变性高度依赖于pH和缓冲液 混合物.