Perera M I, Demetris A J, Katyal S L, Shinozuka H
Cancer Res. 1985 Jun;45(6):2533-8.
The effects of varying the type of dietary fat in the choline-deficient (CD) diet on the development of gamma-glutamyltranspeptidase (GGT)-positive foci in the liver of carcinogen-treated rats were investigated, and the results were correlated with the extent of membrane lipid peroxidation induced by the diets. Male Sprague Dawley rats were initiated with a single dose of diethylnitrosamine. Thereafter, groups of rats were fed choline-supplemented or CD diets in which the amount of saturated fat was varied by using hydrogenated vegetable oil (Primex) and corn oil (CO), either alone or in combination. The number and size of GGT-positive foci induced by the CD diet with CO as the sole source of fat were larger than those induced by the diet containing mixtures of Primex and CO. The CD diet with Primex alone was the least effective in inducing GGT-positive foci. Peroxidation of liver microsomal membrane lipids in rats fed regular CD or CD:CO diets was examined by determining the formation of conjugated dienes. The generation of diene conjugate in rats fed a CD:CO diet was evident after 2 days of the diet feeding, and the levels increased at 1 and 2 weeks. No significant diene conjugate was demonstrated in rats fed a regular CD diet for 2 days. However, after 1 and 2 weeks, there was generation of diene conjugate, the levels of which were lower in rats fed the CD diet than those on a CD:CO diet. Addition of an antioxidant, 0.25% butylated hydroxytoluene, to both CD and CD:CO diets abolished the generation of diene conjugate in rat liver microsomal membranes and markedly inhibited the promotion of GGT-positive foci in the liver of diethylnitrosamine-initiated rats. The results suggest that membrane lipid peroxidation in the liver may be related to the promotion of the induction of GGT-positive foci by a CD diet. The enhanced promotion by the inclusion of a higher level of polyunsaturated fat in the diet may be, in part, due to its greater susceptibility to peroxidation.
研究了在胆碱缺乏（CD）饮食中改变膳食脂肪类型对致癌物处理大鼠肝脏中γ-谷氨酰转肽酶（GGT）阳性灶发展的影响，并将结果与饮食诱导的膜脂质过氧化程度相关联。雄性Sprague Dawley大鼠单次注射二乙基亚硝胺进行启动。此后，将大鼠分组，喂食补充胆碱的饮食或CD饮食，其中通过使用氢化植物油（Primex）和玉米油（CO）单独或组合来改变饱和脂肪的量。以CO作为唯一脂肪来源的CD饮食诱导的GGT阳性灶的数量和大小大于含有Primex和CO混合物的饮食诱导的数量和大小。仅含Primex的CD饮食在诱导GGT阳性灶方面效果最差。通过测定共轭二烯的形成来检查喂食常规CD或CD:CO饮食的大鼠肝脏微粒体膜脂质的过氧化情况。喂食CD:CO饮食的大鼠在饮食喂养2天后共轭二烯生成明显，在1周和2周时水平升高。喂食常规CD饮食2天的大鼠未显示出明显的共轭二烯。然而，在1周和2周后，有共轭二烯生成，喂食CD饮食的大鼠中其水平低于喂食CD:CO饮食的大鼠。在CD和CD:CO饮食中添加抗氧化剂0.25%丁基羟基甲苯消除了大鼠肝脏微粒体膜中共轭二烯的生成，并显著抑制了二乙基亚硝胺启动的大鼠肝脏中GGT阳性灶的促进作用。结果表明，肝脏中的膜脂质过氧化可能与CD饮食促进GGT阳性灶的诱导有关。饮食中包含较高水平的多不饱和脂肪导致的促进作用增强可能部分归因于其对过氧化的更大敏感性。
