FALSE MOREL HYDRAZINES--CARCINOGENESIS AND CHEMISTRY

假羊肚菌肼——致癌作用和化学

基本信息

批准号：
3186622
负责人：
BELA TOTH
金额：
$ 5.42万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-01-01 至 1991-06-30
项目状态：
已结题

项目摘要

More than 100,000 people in the United States annually consume the edible false morel mushroom, Gyromitra esculenta (GE). This fungus contains 11 hydrazine analogues, of which acetaldehyde methylformylhydrazone (AMFH), pentanal methylformylhydrazone (PMFH), N-methyl-N-formylhydrazine (MFH), and N-methylhydrazine (MH) were shown to be carcinogenic in mice in this laboratory. In the present grant, we have set up the carcinogenesis experiments and all have progressed well. The GE feeding induced tumors in the lungs, blood vessels, forestomachs, and cecums of mice. 3Methylbutanal N-methyl-N-formylhydrazone (3-MBMFH) and hexanal N-methyl-N-formylhydrazone (HMFH) have already induced statistically significant incidences of tumors in the lungs, preputial glands, and liver. Also, possible metabolic intermediates derived from MFH that could act as the ultimate carcinogenic species have been identified by studying the oxidative degradation of this hydrazine. Products that form under chemically oxidizing conditions have been identified, too. In this proposal, we intend to continue (1) to determine the tumor-inducing ability of the fresh GE by a lifelong feeding study in mice, (2) to study the tumorigenicity of 3-MBMFH and HMFH ingredients of the mushroom by lifelong oral administration to mice, (3) to measure chemically the amounts of AMFH, MFH, and MH in the mushroom used for the feeding experiment, and (4) to investigate the electrochemical oxidation of WH, MH, and formylhydrazine (FH) through the use of radical trapping agents. 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 (the most potent carcinogen of this series). In a recent study, a variety of tumors were induced in animals fed another fresh mushroom, the cultivated Agaricus bisporus. The proposed experiments likely will provide positive findings in a field of current interest. Virtually nothing is known about the mechanism of action of these highly carcinogenic hydrazines. Our proposed studies should identify the oxidative processes involves. No new studies are proposed. Only the completion of previously approved investigations are requested.

美国每年有100,000多人消费可食用假羊水蘑菇，陀螺仪esculenta（ge）。这个真菌包含11 氢氮类似物，其中乙醛甲醛甲基甲基氢氮酮（AMFH），五甲基甲基甲基氢唑（PMFH），N-甲基-N-甲基氢嗪（MFH），MFH），在此中，N-甲基氢嗪（MH）在小鼠中被证明是致癌的实验室。在目前的赠款中，我们已经建立了癌变实验，所有实验都进展顺利。 GE喂养诱导的肿瘤小鼠的肺，血管，Forestomachs和Cecums。 3methylbutanal N-甲基-N-甲基氢氮酮（3-MBMFH）和己酸N-甲基-N-甲基氢唑酮（HMFH）已经引起肿瘤的统计学意义发生率在肺部，前腺和肝脏中。另外，可能的代谢源自MFH的中间体可以充当最终的致癌通过研究了该物种的氧化降解来识别物种氢氮。在化学氧化条件下形成的产品具有也被确定了。在此提案中，我们打算继续（1）通过终生进食来确定新鲜GE的肿瘤诱导能力在小鼠中的研究，（2）研究3-MBMFH和HMFH的肿瘤性通过终生口服给小鼠的蘑菇成分，（3）用蘑菇中使用的AMFH，MFH和MH的AMFH，MFH和MH的量用于进食实验，（4）研究电化学通过使用自由基的WH，MH和甲基氢嗪（FH）的氧化捕获代理。拟议的研究结果将使我们能够确定蘑菇消费及其的环境意义毒素并揭示三个主要致癌的作用机理氢氮津，特别是MFH（该系列中最有效的致癌物）。在最近的一项研究中，在喂养另一个的动物中诱导了多种肿瘤新鲜的蘑菇，栽培的agaricus bisporus。提出的实验可能会在当前感兴趣的领域提供积极的发现。几乎没有关于这些行动机制的知识致癌氢援助。我们提出的研究应确定氧化剂过程涉及。没有提出新的研究。仅完成请求先前批准的调查。