DIET MODIFICATION & PROMOTION OF LIVER CARCINOGENESIS

在过去几年的支持中，我们证明了 胆碱缺乏(Cd)饮食在诱发肺癌中的致癌作用 几种致癌物引起的肝肿瘤主要是通过其 推动行动。几个代理或修改 Cd饮食的促进作用已经被确认，并且修饰剂 分析了Cd饮食作为促进剂的作用机制。 我们推测，在肝脏肿瘤中，促进剂涉及两个成分；a 刺激启动细胞的增殖和抑制 非启动细胞的增殖。在续期申请中，我们 将用CD的推广方案来检验这一概念的有效性 饮食加巴比妥酸盐对启动的肝脏。的其他几个修饰符 将探索CD饮食推广，如改变脂肪质量 在饮食中，丁基羟基甲苯和一种降血压药物，以及 将试图描述造成这种情况的因素(S)。 修改，包括可能存在不同阶段的 促进肝脏肿瘤。癌前病变假说的回归性质 将调查焦点，以及促进剂在 将对病灶的复发进行评估。最后，饮食上的改变 胆碱缺乏将被用来研究血中胆碱的顺序变化 甲基吡喃的致癌作用，并分析胆管细胞癌 肝细胞癌是通过常见的癌前病变发展起来的 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 肝脏及其营养改良剂。

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.