Sugie S, Tanaka T, Mori H, Reddy B S
Department of Pathology, Gifu University School of Medicine, Japan.
Cancer Lett. 1993 Jan 15;68(1):67-73. doi: 10.1016/0304-3835(93)90221-t.
The modifying effect of 30% caloric restriction on the occurrence of azoxymethane (AOM)-induced glutathione S-transferase placental form (GST-P) positive hepatocellular foci was investigated in male F344 rats. Starting at 5 weeks of age, groups of animals were fed ad libitum a high-fat (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were s.c. injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). Four days after the second injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) consumed by the ad libitum group, but received the same amounts of fiber, vitamins and minerals. Thirty-two weeks after AOM injections, all animals were necropsied and livers were sectioned and stained for GST-P by a immunohistochemical technique for quantitative analysis of enzyme altered foci of the liver. Comparing AOM treated groups. The density and the unit area of enzyme altered foci were significantly lower in the calorie-restricted group (3.84 +/- 1.55/cm2, 7.96 +/- 5.43%) than in the ad libitum group (10.14 +/- 3.62/cm2, 28.11 +/- 12.33%). The size of foci was also reduced in the calorie-restricted group (17.15 x 10(-3) mm2 vs. 32.36 x 10(-3) mm2). The incidence and density of hepatocellular foci in rats fed calorie restricted diet were significantly lower than those in rats fed ad libitum, comparing vehicle-treated groups. These results indicate that calorie restriction inhibited the occurrence of both of spontaneous and AOM induced GST-P positive foci in rats.
在雄性F344大鼠中研究了30%热量限制对偶氮甲烷(AOM)诱导的谷胱甘肽S-转移酶胎盘型(GST-P)阳性肝细胞灶发生的影响。从5周龄开始,将动物分组自由采食高脂肪(23.5%)半纯化日粮。7周龄时,除溶剂处理组外的所有动物均皮下注射AOM(15mg/kg体重,每周1次,共2周)。第二次注射后4天,将动物分组继续给予高脂肪日粮并自由采食(自由采食组),而其他组则限制采食至自由采食组所摄入总热量的70%(热量限制组),但给予相同量的纤维、维生素和矿物质。AOM注射32周后,对所有动物进行尸检,将肝脏切片并用免疫组织化学技术对GST-P进行染色,以对肝脏中酶改变灶进行定量分析。比较AOM处理组。热量限制组中酶改变灶的密度和单位面积(3.84±1.55/cm2,7.96±5.43%)显著低于自由采食组(10.14±3.62/cm2,28.11±12.33%)。热量限制组中灶的大小也减小(17.15×10⁻³mm²对32.36×10⁻³mm²)。比较溶剂处理组,热量限制饮食喂养的大鼠中肝细胞灶的发生率和密度显著低于自由采食的大鼠。这些结果表明,热量限制抑制了大鼠自发性和AOM诱导的GST-P阳性灶的发生。