CARCINOGENESIS AND CHEMISTRY OF CULTIVATED MUSHROOMS

双孢蘑菇（Agaricus bisporus，AB）是商业上栽培的蘑菇，含有 几个肼和重氮离子。 我们早些时候报道说， 这些化合物，N ′-乙酰基-4-（羟甲基）苯肼和 4-（羟甲基）重氮苯四氟硼酸，诱导肿瘤在五个 瑞士老鼠的组织。 我们证明了硫酸盐的致癌性 重氮离子的形式，从而降低了重氮离子 四氟硼酸盐作为共致癌物。 另外我们有 首次令人信服地证明了两个肼的存在 对肼基苯甲酸和 蘑菇中的β-N-[γ-L（+）-谷氨酰]-4-羧基苯肼。 此外，使用细胞色素P-450混合功能氧化酶和 前列腺素（H）合酶，我们证明了在体外代谢 几种蘑菇肼，这导致的可能性， 反应性致癌代谢物可在细胞内产生。 研究 也在进行中，以证明两种可能的致癌性， 另外的蘑菇肼，以及蘑菇本身，以及 揭示了芳烃重氮盐与脱氧核苷的反应， DNA. 在新的提案中，我们计划将研究扩展到：1）重新调查 4-（羟基薄荷基）重氮苯硫酸盐的致癌活性 在MTD和MTD的分数下通过管饲法; 2）确定可能的 两种肼衍生物在小鼠中的致瘤性： β-N-[γ-L（+）-谷氨酰基]-4-甲酰基苯肼和 β-N-[γ-L（+）谷氨酰基]-4-甲基苯肼， 蘑菇碱生物合成中的中间体; 3）分析我们使用 放射性标记的化合物中存在的其他肼，假设 蘑菇碱前体的研究和比较 细胞色素P-450和前列腺素（H）合酶对蘑菇肼的影响 从靶器官和非靶器官; 5）研究 γ-谷氨酰转肽酶在各种烹饪条件下模拟 人体接触条件; 6）合成上述和其他化学品 用于分析生化、毒性和致癌性研究。 这些研究的积极发现将使我们有可能 一些人类癌症可能是由这些天然成分引起的 人类的饮食。 此外，还提出了关于 蘑菇肼和相关化学物质的作用可能有助于 阐明和理解致癌作用的分子基础。 的 据估计，美国的AB消费总量约为2.8亿美元 1981 - 1982年，

Agaricus bisporus (AB), the cultivated mushroom of commerce, contains several hydrazines and a diazonium ion. We reported earlier that two of these compounds, the N'-acetyl-4-(hydroxymethyl)phenylhydrazine and the 4-(hydroxymethyl)benzenediazonium tetrafluoroborate, induced tumors in five tissues of Swiss mice. We demonstrated the carcinogenicity of the sulfate form of the diazonium ion, thus discounting the possibility that the tetrafluoroborate salt acted as a co-carcinogen. In addition, we have convincingly shown for the first time the presence of two hydrazines p-hydrazinobenzoic acid and beta-N-[gamma-L(+)-glutamyl]-4-carboxyphenylhydrazine in the mushroom. Furthermore, using cytochrome P-450 mixed function oxidases and prostaglandin (H) synthase enzyme, we demonstrated in vitro the metabolism of several mushroom hydrazines, which leads to the possibility that reactive carcinogenic metabolites can be produced intracellularly. Studies are also underway to demonstrate the possible carcinogenicity of two additional mushroom hydrazines, as well as of the mushroom itself, and to reveal the reactions of arenediazonium salts with deoxynucleosides and DNA. In the new proposal we plan to extend our studies to 1) reinvestigate the cancer-inducing ability of 4-(hydroxymenthyl)benzenediazonium sulfate by gavage at MTD and fractions of MTD; 2) determine the possible tumorigenicity in mice of two hydrazine derivatives: beta-N-[gamma-L(+)-glutamyl]-4-formylphenylhydrazine and beta-N-[gamma-L(+)glutamyl]-4-methylphenylhydrazine, the postulated intermediates in agaritine biosynthesis; 3) analyze AB grown by us using radiolabeled compounds for the presence of other hydrazines, the postulated precursors of agaritine; 4) study and compare the metabolism and activation of mushroom hydrazines by cytochrome P-450 and prostaglandin (H) synthase from target and non-target organs; 5) investigate the activity of gamma-glutamyl-transpeptidase under various cooking conditions mimicking the human exposure conditions; 6) synthesize the above and other chemicals for analytical biochemical, toxicity and carcinogenicity investigations. Positive findings from these studies would lead us to the possibility that some human cancer could be caused by these naturally occurring ingredients of the human diet. In addition, the proposed studies on the mechanism of action of the mushroom hydrazines and related chemicals might help to elucidate and to understand the molecular basis of carcinogenesis. The estimated US AB consumption totaled approximately over 280 million kilograms in 1981-82.