TRYPTOPHAN AND HEPATIC CARCINOGENESIS

这项提案的目标是调查提升了 饮食中的色氨酸可能在肝脏过程中起促进作用 肿瘤发生学。基于其他人和我们的实验研究， L-色氨酸已被证明可增强诱发肝癌的发生 被选定的致癌物。我们计划将注意力集中在如何 饮食中增加的色氨酸起着促进剂的作用。鉴于之前的 其他人和我们的研究结果表明，L-色氨酸对 控制肝脏多聚核糖体和蛋白合成，我们计划探索 这些影响中的一些是否会在促销期间产生影响。我们 L-色氨酸在肝癌发生中可能起启动子作用的假设 通过刺激肝脏中核浆内的信使核转位。是这样的 启蒙过程后的刺激(如通过给药 二乙基亚硝胺(二乙基亚硝胺)可能导致 出现更多γ-谷氨酰转肽酶阳性的肝细胞和 最终更多的是肝细胞癌。与此相关的研究 核膜的过程和变化，特别是蛋白质 (糖蛋白，如层蛋白B)，是计划的。此外，我们计划 研究色氨酸可能作为启动子的其他可能方式，例如 可能通过影响细胞坏死和/或细胞增殖，通过 降低肝脏谷胱甘肽水平，或通过在 胃肠道与亚硝酸盐形成致癌化合物。

The objective of this proposal is to investigate the role that elevated dietary tryptophan may play in promotion during the course of liver tumorigenesis. Based upon experimental studies by others and by us, L-tryptophan has been demonstrated to enhance liver carcinogenesis induced by selected hepatocarcinogens. We plan to focus our attention on how elevated dietary tryptophan acts as a promoter. In view of previous findings by others and by us that L-tryptophan has unique actions on the control of hepatic polyribosomes and protien synthesis, we plan to explore whether some of these effects are influential during promotion. We hypothesize that L-tryptophan may act as a promoter in liver carcinogenesis by stimulating nucleocytoplasmic translocation of mRNA in the liver. Such stimulation directed after the process of initiation (as by administering diethylnitrosamine shortly after subtotal hepatectomy) may lead toward the emergence of more Gamma-glutamyltranspeptidase positive hepatocytes and ultimately more hepatocellular carcinomas. Studies relating to this process and alterations in nuclear membranes, specifically proteins (glycoproteins such as lamin B), are planned. In addition, we plan to investigate other possible ways tryptophan may act as promoter, such as possibly by affecting cell necrosis and/or cell proliferation, by diminishing liver glutathione levels, or by reacting in the gastrointestinal tract with nitrites to form carcinogenic compounds.