CARCINOGENESIS AND CHEMISTRY OF CULTIVATED MUSHROOMS

双孢菇(Agaricus biporus(AB))，栽培食用菌，含有 几种肼和一种重氮离子。我们早些时候报道过，其中两个 这些化合物是N‘-乙酰基-4-(羟甲基)苯肼和 4-(羟甲基)苯重氮四氟硼酸盐诱发肿瘤5例 瑞士小鼠的组织。我们证明了硫酸盐的致癌性。 以重氮离子的形式存在，从而排除了 四氟硼酸盐是一种共同致癌物质。此外，我们还有 首次令人信服地证明了两种肼的存在 对氨基苯甲酸和 蘑菇里的beta-N-[gamma-L(+)-glutamyl]-4-carboxyphenylhydrazine。 此外，使用细胞色素P-450混合功能氧化酶和 前列腺素(H)合成酶，我们在体外演示了代谢 几种蘑菇肼，这导致了 活性致癌代谢物可以在细胞内产生。研究 也在进行中，以证明两种物质可能的致癌性 添加蘑菇肼，以及蘑菇本身，并 揭示了芳基重氮盐与脱氧核苷的反应 DNA在新的提案中，我们计划将我们的研究扩展到1)重新调查 4-(羟基薄荷基)苯重氮硫酸盐的致癌作用 通过灌胃MTD和MTD的分数；2)确定可能的 两种肼类化合物对小鼠的致瘤性 Beta-N-[gamma-L(+)-glutamyl]-4-formylphenylhydrazine和 假设的beta-N-[gamma-L(+)glutamyl]-4-methylphenylhydrazine， 蘑菇菌素生物合成的中间体；3)分析我们种植的AB 假定存在其他肼的放射性标记化合物 阿糖胞苷前体物；4)代谢和激活的研究和比较 细胞色素P-450和前列腺素(H)合成酶对蘑菇肼的作用 从靶器官和非靶器官；5)调查 不同蒸煮条件下的γ-谷氨酰转肽酶 人体暴露条件；6)合成上述及其他化学物质 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 某些人类癌症可能是由这些天然成分引起的。 人类饮食的一部分。此外，拟开展的关于黄曲霉毒素的作用机制的研究 蘑菇肼和相关化学物质的作用可能有助于 阐明和理解致癌的分子基础。这个 据估计，美国AB的总消费量约超过2.8亿 在1981-82年间。

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.