ETHIONINE CARCINOGENESIS

蛋氨酸类似物蛋氨酸是一种大鼠肝癌原。 之一 乙烯利的主要代谢产物是S-腺苷乙烯利（S-腺苷乙烯利）， 是S-腺苷甲硫氨酸（腺苷甲硫氨酸）的类似物。 脂肪酸在 急性或慢性给药时大鼠的肝组织， 怀疑在乙醇致癌作用中起主要作用。 我们计划 研究蛋氨酸和乙烯利的合成和细胞分布， 各种致癌模型。 组织特异性将在 老鼠 将使用大鼠、仓鼠、 小鼠和豚鼠。 在本说明书中还将研究羟乙基醚的合成。 动物喂食无胆碱的0.05%乙醇饮食。 还已经 从我们的实验室证明，乙烯利通过乙烯利抑制DNA， 产生低甲基化状态的蛋白质甲基化酶。 DNA和蛋白质 甲基化将通过给予[3 H-甲基]-甲硫氨酸在体内进行研究， 体外用甲基化酶的酶测定，并通过使用 限制性内切核酸酶。 肉毒杆菌对仓鼠没有致癌性， 因此，对大鼠和仓鼠的比较研究应该能提供更好的 理解在基因治疗中对低甲基化DNA和/或蛋白质的需要 致癌作用 这项工作的总体长期目标是 逐步破译化学物质的生化机制， 致癌作用 直接的工作涉及乙醇的致癌作用， 工作模式。

Ethionine, a methionine analog, is a hepatocarcinogen in the rat. One of the major metabolites of ethionine is S-adenosylethionine (AdoEth), which is an analog of S-adenosylmethionine (AdoMet). AdoEth accumulates in the hepatic tissue of rats when given acutely or chronically and has been suspected to play a major role in ethionine carcinogenesis. We plan to study the synthesis and cellular distribution of AdoMet and AdoEth in various carcinogenic models. The tissue specificity will be examined in the rat. Species differences will be studied using the rat, hamster, mouse, and guinea pig. The synthesis of AdoEth will also be examined in animals fed a choline-devoid-0.05% ethionine diet. It has also been demonstrated from our laboratory that ethionine via AdoEth inhibits DNA and protein methylases producing a hypomethylated state. DNA and protein methylation will be studied in vivo by giving [3H-methyl]-methionine, in vitro with an enzymatic assay for the methylase enzymes, and by the use of restriction endonucleases. Ethionine is not carcinogenic to the hamster, therefore a comparative study of the rat and hamster should give a better understanding of the need for hypomethylated DNA and/or protein in carcinogenesis. The overall long term objective of this work is to decipher in a stepwise manner the biochemical mechanism of chemical carcinogenesis. The immediate work involves ethionine carcinogenesis as the working model.