CARCINOGENESIS AND CHEMISTRY OF THE CULTIVATED MUSHROOMS

通常食用的栽培蘑菇，双孢蘑菇（AB），含有 几种含N-N键的化学物质 我们之前演示了 其中一些蘑菇的存在、致癌性和作用方式 化学品 在最近的拨款中，我们已经证明了 生蘑菇和它的一些成分在长期的实验中 对小鼠 此外，我们还发现了两种肼的存在： 对肼基苯甲酸和β-N-[γ L（+）-谷氨酰基]-4- 蘑菇提取物中的羧基苯肼。 我们还 证明了在体外代谢的几个蘑菇芳基肼 使用细胞色素P-450混合功能氧化酶和前列腺素（H） 合成酶 最后，使用嘌呤碱基和核苷，我们得到 模拟了4-羟甲基重氮苯离子（HMBD）的反应 并观察到HMBD可以与DNA反应。 二次 反应（例如，交联）可能是重要的。 最后，我们决定 烘烤后蘑菇中肼的含量：只有25%， 摧毁. 此外，使用艾姆斯试验，我们注意到没有显着差异 烤蘑菇和未烤蘑菇的致突变活性 萃取物 在这一新的持续提案中，我们打算扩大我们的 调查：（1）研究烘焙，冻干的致癌性 和原始AB通过使用剂量反应协议在终身实验中， （2）研究了4-羟基重氮苯的致瘤性 小鼠中硫酸盐;（3）使用放射性标记化合物分析我们培养AB 重氮离子和肼的存在;（4）确定 HMBD、其他重氮离子及其反应性产物 在生理pH值下，在体外用碱基、核苷和DNA对物种进行修饰， 在分离的细胞中;和（5）合成上述和其它化学品， 分析化学、生物化学和致癌性研究。 积极 该项目的研究结果可能具有实际意义，因为 人类主要食用烤蘑菇。 此外，机制研究 蘑菇肼和相关化学物质的研究可能有助于揭示 分子水平上的作用模式。 每年估计的蘑菇 美国的消费量约为4.35亿公斤 在1990-91年。 西欧的相应数字超过644 百万公斤。

The commonly eaten, cultivated mushroom, Agaricus bisporus (AB), contains several N-N-bond-containing chemicals. We demonstrated earlier the presence, carcinogenicity and mode of action of some of these mushroom chemicals. In the recent grant, we have shown the carcinogenicity of the uncooked mushroom and some of its ingredients in long-term experiments in mice. In addition, we have revealed the presence of two hydrazines: p-hydrazinobenzoic acid and beta-N-[gammaL(+)-glutamyl]-4- carboxyphenylhydrazine in the mushroom extracts. Further, we demonstrated in vitro the metabolism of several mushroom arylhydrazines using cytochrome P-450 mixed function oxidases and prostaglandin (H) synthase enzymes. Finally, using purine bases and nucleosides, we have modeled the reactions of 4-(hydroxymethyl)benzenediazonium ion (HMBD) with DNA and have observed that HMBD can react with DNA. Secondary reactions (e.g., cross-linking) may be important. Lastly, we determined the amount of hydrazines in the mushroom after baking: Only 25% was destroyed. Also, using the Ames assay we noted no significant difference between the mutagenic activities of the baked and unbaked mushroom extracts. In this new continuing proposal, we intend to extend our investigations to: (1) study the carcinogenicity of baked, lyophilized and raw AB by using a dose response protocol in lifelong experiments in mice; (2) reveal the tumorigenicity of 4-(hydroxy-benzenediazonium sulfate in mice; (3) analyze AB grown by us using radiolabeled compounds for the presence of diazonium ions and hydrazines; (4) determine the products of the reaction of HMBD, other diazonium ions and their reactive species with bases, nucleosides and DNA in vitro at physiological pH and in isolated cells; and (5) synthesize the above and other chemicals for analytical chemistry, biochemical and carcinogenicity studies. Positive findings from this project might have practical implications, because humans consume mainly baked mushrooms. Further, the mechanistic studies on mushroom hydrazines and related chemicals might help to reveal their mode of action on the molecular level. The annual estimated mushroom consumption in the United States was approximately 435 million kilograms in 1990-91. The corresponding figure in western Europe was more than 644 million kilograms.