CARCINOGENESIS AND CHEMISTRY OF THE CULTIVATED MUSHROOMS

栽培蘑菇的致癌作用和化学成分

• 批准号: 2088153
• 负责人: BELA TOTH
• 金额: $ 19.11万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-01 至 1996-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2088153
• 关键词: Agaricales; DNA; adduct; albino mouse; analytical chemistry; chemical carcinogenesis; diazo compound; food processing /preparation; lyophilization; mass spectrometry; mutagen testing; nuclear magnetic resonance spectroscopy; nucleobase; nucleosides; nutrient interaction; nutrition related tag; personal computers; phenylhydrazines; plant extracts; radiotracer; tissue /cell culture; toxin metabolism; ultraviolet spectrometry

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.

通常食用的，栽培的蘑菇，agaricus bisporus（AB）包含 几种含N-N键的化学物质。 我们以前证明了 其中一些蘑菇的存在，致癌性和作用方式 化学物质。 在最近的赠款中，我们显示了 在长期实验中未煮过的蘑菇及其成分 在老鼠中。 此外，我们已经揭示了两个氢援氮的存在： p-羟基苯甲酸和β-n- [gammal（+） - 谷氨酰基] -4- 蘑菇提取物中的羧苯基氢嗪。 此外，我们 在体外证明了几种蘑菇芳基水氮的代谢 使用细胞色素P-450混合功能氧化酶和前列腺素（H） 合酶。 最后，使用嘌呤碱和核苷，我们有 建模了4-（羟甲基）苯基二氮酮离子（HMBD）的反应 使用DNA并观察到HMBD可以与DNA反应。 次要 反应（例如，交联）可能很重要。 最后，我们确定 烘烤后，蘑菇中的氢氮津含量：只有25％ 被摧毁。 另外，使用AMES分析我们没有明显的差异 在烘焙和未烤的蘑菇的诱变活动之间 提取物。 在这个新的持续提案中，我们打算扩展我们的 调查：（1）研究烘焙，冻干的致癌性 通过在终身实验中使用剂量响应方案的RAW AB 小鼠； （2）揭示了4-（羟基苯二氮二氮的肿瘤性 小鼠硫酸盐； （3）使用放射性标记的化合物分析我们生长的AB 对于格锌离子和肼的存在； （4）确定 HMBD，其他重点离子及其反应性的反应产物 具有碱基，核苷和DNA的物种在生理pH和 在孤立的细胞中； （5）合成上述化学物质和其他化学物质 分析化学，生化和致癌性研究。 积极的 该项目的发现可能具有实际含义，因为 人类主要食用蘑菇。 此外，机械研究 在蘑菇弹药和相关化学物质上可能有助于揭示其 分子水平上的作用方式。 年度估计蘑菇 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。