DIET MODIFICATION & PROMOTION OF LIVER CARCINOGENESIS

在过去几年的支持中，我们证明， 胆碱缺乏（CD）饮食在诱导 几种致癌物主要通过其介导的肝肿瘤 促进行动。 几个代理或条件，修改 CD饮食的促进功效已经被证实，并且调节剂 分析CD饮食作为促进剂的作用机制。 我们假设，在肝肿瘤促进两个成分参与; 刺激起始细胞的增殖和抑制 非起始细胞的增殖。 在更新申请中，我们 我将用CD的推广方案来检验这一概念的有效性 饮食加巴比妥类药物治疗。 其他几个修饰语 将探索CD饮食促进，例如改变脂肪的质量， 在饮食中，丁羟甲苯和降血脂药物， 将尝试描述导致 修改，包括可能存在的分离阶段， 肝肿瘤促进。 退化性假定的癌前病变的性质 焦点将被调查，和促进剂的作用， 将评估病灶的复发。 最后， 胆碱缺乏将被应用于调查的顺序变化， methapyrilene致癌作用，并分析是否胆管癌 而肝细胞癌是通过常见的癌前病变 前驱病变 希望拟议的研究将提供 与肿瘤促进机制相关的最新信息， 肝脏及其营养变化。

During the past years of the support, we demonstrated that the cocarcinogenic effect of a choline-deficient (CD) diet in the induction of liver tumors by several carcinogens is primarily mediated through its promoting action. Several agents or the conditions which modify the promoting efficacy of the CD diet have been idenfified, and the modifiers were used to nalyze the mechanisms of action of the CD diet as a promoter. We postulated that in liver tumor promoting two components are involved; a stimulation of the proliferation of initiated cells and a suppression of the proliferation of non-initiated cells. In the renewal application, we will test the validity of this concept with the promotion regimen of a CD diet plus barbiturates on the initiated liver. Several other modifiers of the CD diet promotion will be explored, such as altering the quality of fat in the diet, butylated hydroxytoluene and a hypolipedemic drug, and attempts will be made to characterize factor(s) responsible for the modifications, including a possible presence of separate stages of the liver tumor promotion. The nature of regressing putative preneoplastic foci will be investigated, and roles of the promoting agents in the resurgence of foci will be evaluated. Finally, the dietary modification of choline deficiency will be applied to investigate the sequential changes of methapyrilene carcinogenesis, and to analyze whether cholangiocarcinomas and hepato-cellular carcinomas develop through common preneoplastic precursor lesions. It is hoped that the proposed studies will provide newer information relevant to the mechanisms of tumor promotion in the liver and its nutritional modifications.