Baldwin S, Parker R S
Carcinogenesis. 1987 Jan;8(1):101-7. doi: 10.1093/carcin/8.1.101.
Aflatoxin B1-induced hepatic gamma-glutamyl transpeptidase-positive foci were quantified in rats fed different levels of fat and selenium during either initiation or early promotion. Male Sprague-Dawley rats were divided into 12 groups. One of six experimental diets were fed to groups 1-6 prior to and during aflatoxin B1 exposure (initiation, weeks 1-4.5) and to groups 7-12 during weeks 4.5-15 (promotion). The six experimental diets contained 2 or 20% corn oil, each with either less than 0.02, 0.15 or 2.5 (or 1.9) p.p.m. selenium. When not fed the experimental diets, rats were fed a modified AIN-76A diet. In groups 1-6, 0.03% phenobarbital was added as a promoter to the AIN-76A diet. Individual and interactive effects of selenium and fat were dependent on the stage of carcinogenesis. High dietary fat fed with either less than 0.02 or 0.15 p.p.m. selenium during initiation resulted in a significant increase in the number and size of foci when compared with low fat groups. In rats fed 20% fat and 2.5 p.p.m. selenium during initiation, preneoplastic development was reduced below all low fat groups. In contrast, selenium status but not dietary fat level influenced focal formation during promotion. Rats fed less than 0.02 p.p.m. selenium had a significantly greater percentage of liver section occupied by foci than rats fed either 0.15 or 1.9 p.p.m. selenium. Feeding 1.9 p.p.m. selenium during promotion did not afford greater protection above the 0.15 p.p.m. level. Hepatic glutathione peroxidase activity at week 15 was significantly diminished in animals fed less than 0.02 p.p.m. selenium during promotion. Feeding 1.9 p.p.m. selenium when compared with 0.15 p.p.m. did not result in a consistent increase in enzyme activity. Although differences were observed in growth due to dietary treatment, there were no significant correlations between preneoplastic foci and body weight, food consumption or food efficiency. These findings indicate an interaction between dietary fat and selenium during initiation, but not during early promotion. Furthermore, dietary selenium and fat may function by different mechanisms at different stages of carcinogenesis.
对在启动期或早期促癌阶段饲喂不同脂肪和硒水平的大鼠，定量检测黄曲霉毒素B1诱导的肝脏γ-谷氨酰转肽酶阳性病灶。将雄性斯普拉格-道利大鼠分为12组。在黄曲霉毒素B1暴露之前及暴露期间（启动期，第1 - 4.5周），给第1 - 6组饲喂六种实验日粮中的一种，在第4.5 - 15周（促癌期）给第7 - 12组饲喂其中一种。六种实验日粮含2%或20%玉米油，每种玉米油分别添加低于0.02、0.15或2.5（或1.9）ppm的硒。大鼠不喂实验日粮时，饲喂改良的AIN - 76A日粮。在第1 - 6组中，向AIN - 76A日粮中添加0.03%苯巴比妥作为促癌剂。硒和脂肪的个体及交互作用取决于致癌作用阶段。启动期饲喂低于0.02或0.15 ppm硒的高膳食脂肪，与低脂组相比，病灶数量和大小显著增加。启动期饲喂20%脂肪和2.5 ppm硒的大鼠，癌前病变发展低于所有低脂组。相反，促癌期病灶形成受硒状态影响，而不受膳食脂肪水平影响。饲喂低于0.02 ppm硒的大鼠，病灶占据肝脏切片的百分比显著高于饲喂0.15或1.9 ppm硒的大鼠。促癌期饲喂1.9 ppm硒并未比0.15 ppm水平提供更大保护。促癌期饲喂低于0.02 ppm硒的动物，第15周时肝脏谷胱甘肽过氧化物酶活性显著降低。与0.15 ppm相比，饲喂1.9 ppm硒并未使酶活性持续增加。尽管观察到因膳食处理导致生长有差异，但癌前病灶与体重、食物消耗或食物效率之间无显著相关性。这些发现表明启动期膳食脂肪与硒之间存在交互作用，但早期促癌阶段不存在。此外，膳食硒和脂肪在致癌作用的不同阶段可能通过不同机制发挥作用。
