FALSE MOREL HYDRAZINES--CARCINOGENESIS AND CHEMISTRY

美国每年有超过10万人食用这种可食用的 假羊肚菌Gyromitra esculenta（GE）。这种真菌含有11 肼类似物，其中乙醛甲酰基腙（AMFH）， 戊醛甲基甲酰腙（PMFH），N-甲基-N-甲酰肼（MFH）， 和N-甲基肼（MH）被证明是致癌的小鼠在这一点上， 实验室在目前的拨款中，我们设立了致癌作用 实验和一切都进展顺利。GE喂养诱导肿瘤， 小鼠的肺、血管、前胃和盲肠。3-甲基丁醛 N-甲基-N-甲酰腙（3-MBMFH）和己醛N-甲基-N-甲酰腙 （HMFH）已经诱导了统计学上显著的肿瘤发生率， 在肺包皮腺和肝脏还有可能是新陈代谢 来自MFH的中间体，可能作为最终致癌物 通过研究这种物质的氧化降解， 肼。在化学氧化条件下形成的产物具有 也被认出来了。在本建议中，我们打算继续（1）， 通过终身饲养测定新鲜GE的致瘤能力， （2）研究3-MBMFH和HMFH的致瘤性 通过对小鼠终身口服施用蘑菇的成分，（3） 用化学方法测量所用蘑菇中AMFH、MFH和MH的含量 （4）研究了电化学 通过使用自由基氧化WH、MH和甲酰肼（FH） 诱捕剂拟议研究的结果将使我们能够 确定食用蘑菇的环境意义及其 毒素，并揭示了三种主要致癌物质的作用机制 肼，特别是MFH（这一系列中最强的致癌物）。 在最近的一项研究中，在喂食另一种药物的动物中诱发了多种肿瘤。 新鲜蘑菇，人工栽培的双孢蘑菇。拟议的实验 可能会在当前感兴趣的领域提供积极的发现。 几乎没有什么是已知的作用机制，这些高度 致癌的肼。我们提议的研究应该确定 过程涉及。未提出新的研究。只有完成 要求进行先前批准的调查。

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.