FALSE MOREL HYDRAZINES: CARCINOGENESIS AND CHEMISTRY

假羊肚菌肼：致癌和化学

• 批准号: 3186620
• 负责人: BELA TOTH
• 金额: $ 10.59万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-01 至 1989-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3186620
• 关键词: Agaricales; MAO inhibitors; alkylating agents; amine oxidase (flavin); autoradiography; carcinogen testing; chemical carcinogen; chemical carcinogenesis; cytochrome P450; electrochemistry; gas chromatography; gas chromatography mass spectrometry; guanine; histology; hydrazines; hydrazones; methylhydrazines; methylpurine; microorganism toxicology; monoclonal antibody; mycotoxins; nuclear magnetic resonance spectroscopy; nutrition related neoplasm /cancer; nutrition related tag; oxidation; prostaglandin endoperoxide synthase; radioimmunoassay; thymine; toxin metabolism

Approximately 100,000 people in the U.S.A. annually consume the edible false morel mushroom Gyromitra esculenta. This fungus contains eleven hydrazine analogues, of which acetaldehyde methylformylhydrazone (AMFH), N-methyl-N-formylhydrazine (MFH) and N-methylhydrazine (MH) were shown to be carcinogenic in mice in this laboratory. In this proposal we intend (1) to determine the tumor-inducing ability of the fresh Gyromitra esculenta by a lifelong feeding study in mice, (2) to study the tumorigenicity of 3-methylbutanal N-methyl-N-formylhydrazone and hexanal N-methyl-N-formylhydrazone ingredients of the mushromm by lifelong oral administration to mice, (3) to investigate by repeated weekly intragastric instillations in propylene glycol the carcinogenicity of MFH and MH in mice, (4) to measure chemically the amounts of AMFH, MFH and MH in the mushroom used for the feeding experiment, (5) to study the distribution of AMFH, MFH and MH following administration by gavage in propylene glycol and water using whole-body autoradiography, (6) to investigate the electrochemical oxidation of MFH, MH, and formylhydrazine (FH) with the use of radical trapping agents, (7) to investigate the in vitro and in vivo metabolism of MFH using cytochrome P450, flavin monooxygenase and prostaglandin(H)synthase systems, and (8) to determine the extent and nature of DNA alkylation, with particular emphasis on the formation and persistence of 06-methylguanine and 04-methylthymine using the sensitive monoclonal antibody/radioimmunoassay technique. The results of the proposed study will allow us to determine the environmental significance of mushroom consumption and their toxins and reveal the mechanism of action of the three main carcinogenic hydrazines, particularly MFH (to date the most potent carcinogen of this series). A recent study feeding another fresh mushroom, the cultivated Agaricus bisporus, induced a variety of tumors in animals. The proposed experiments will likely provide positive findings in a field of current high interest. Virtually nothing is known about the mechanism of action of these highly carcinogenic hydrazines. Our proposed studies should identify the oxidative processes and should elucidate the enzyme systems involved.

美国大约有100,000人每年食用可食用 假羊水蘑菇gyomitra esculenta。 这个真菌包含11个 氢氮类似物，其中乙醛甲醛甲基甲基氢氮酮（AMFH）， N-甲基-N-甲基氢嗪（MFH）和N-甲基氢嗪（MH）已显示为 在该实验室中的小鼠中致癌。 在此提案中，我们打算（1） 通过 （2）研究终身喂养研究，以研究 3-甲基丁酸N-甲基-N-甲基氢氮酮和己酮 Mushromm的N-甲基-N-甲基氢援助成分，终身口服 给小鼠的给药，（3）通过重复的每周胃内进行调查 在丙烯中滴注MFH和MH的致癌性 小鼠，（4）以化学测量AMFH，MFH和MH的量 用于进食实验的蘑菇，（5）研究 通过抗丙烯和丙二醇和 使用全身放射自显影的水，（6）研究 使用MFH，MH和甲基氢嗪（FH）的电化学氧化 自由基诱捕剂，（7）研究体内和体内 使用细胞色素P450，黄素单加氧酶和MFH代谢 前列腺素（H）合酶系统，（8）确定程度和 DNA烷基化的性质，特别着重于形成和 使用敏感 单克隆抗体/放射免疫测定技术。 结果 拟议的研究将使我们能够确定 蘑菇消耗及其毒素，并揭示 三个主要的致癌氢援氮，尤其是MFH（迄今为止最多的 该系列的有效致癌物）。 最近的一项喂养另一个新鲜的研究 蘑菇是培养的agaricus bisporus，在 动物。 拟议的实验可能会在 当前高度兴趣的领域。 几乎什么都不知道 这些高度致癌的氢援氮的作用机理。 我们提出的 研究应确定氧化过程，并应阐明 涉及的酶系统。