METABOLIC CONVERSIONS OF AROMATIC AMINES & PATHOGENESIS OF BLADDER CANCER

芳香胺的代谢转化

• 批准号: 6486814
• 负责人: TERRY ZENSER
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486814
• 关键词: biological products; biomedical equipment development; biomedical resource; immunology; inflammation; lipids; nucleic acids; proteins; spectrometry; technology /technique

Aromatic amines, such as benzidine, are thought to induce bladder cancer via pathways involving metabolic activation to reactive species that result in modification of DNA. Over the last five years we have developed a model of benzidine-induced bladder cancer that has depended heavily on identification and quantitation of benzidine metabolites and synthetic standards at the Washington University Mass Spectrometry facility using GC/MS, FAB/MS, high resolution MS, and ESI/MS/MS. Our model is that, in human liver, benzidine is first N-acetylated and then converted to an N/-glucuronide, which is then excreted in urine. In acidic urine, the glucuronide is hydrolyzed to N-acetylbenzidine, which accumulates in bladder epithelial cells and is converted to reactive species by the peroxidase activity of prostaglandin H synthase. These species then form adducts, including N'-(3'-monophospho-deoxyguanosin-8-yl)-N-acetylbenzidine (dGp-ABZ), that cause mutations that initiate ca rcinogenes is. Developing and testing various aspects of this model have required mass spectrometric characterization of the intermediates proposed to be involved in this pathway.

芳香胺，如联苯胺，被认为会诱发膀胱