FALSE MOREL HYDRAZINES--CARCINOGENESIS AND CHEMISTRY

美国每年有超过10万人消费这种可食用食品 假羊肚菌Gyromitra esculenta(GE)。该真菌含有11种 肼类似物，其乙醛甲基甲酰肼(AMFH)， 戊醛甲酰肼(PMFH)、N-甲基-N-甲酰肼(MFH)、 和N-甲基肼(MH)在小鼠中被证明是致癌的 实验室。在目前的拨款中，我们设立了致癌 实验和所有的进展都很好。锗喂养诱发小鼠肿瘤的实验研究 小鼠的肺、血管、前胃和盲肠。3甲基丁醛 N-甲基-N-甲酰肼(3-MBMFH)和己醛 (HMFH)已经导致了统计上显著的肿瘤发病率 在肺、包皮腺和肝脏。此外，可能的代谢 从MFH衍生的中间体可能起到最终致癌作用 通过研究这一物质的氧化降解，已经鉴定了物种 联氨。在化学氧化条件下形成的产品具有 也被确认了身份。在这项建议中，我们打算继续(1) 用终身饲养法测定新鲜锗的致瘤能力 小鼠实验，(2)研究3-MBMFH和HMFH的致瘤性 小鼠终身口服的蘑菇成分，(3)至 用化学方法测量所用蘑菇中AMFH、MFH和MH的含量 用于投料实验，以及(4)电化学研究 WH、MH和甲酰肼(FH)的自由基氧化 诱捕剂。拟议研究的结果将使我们能够 确定蘑菇消费的环境意义及其 并揭示了三种主要致癌物质的作用机制 肼，特别是MFH(本系列中最强的致癌物质)。 在最近的一项研究中，喂食另一种动物的动物诱发了各种肿瘤。 鲜菇，栽培的双孢菇。拟议中的实验 可能会在当前感兴趣的领域提供积极的发现。 事实上，人们对这些高度敏感的物质的作用机制一无所知。 致癌的联氨。我们提议的研究应该确定氧化的 过程涉及到。没有提出新的研究建议。只有在完成 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.