Enhancement of Mammary Carcinogenesis by High Levels of Dietary Fat: A Phenomenon Dependent on Ad Libitum Feeding

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Abstract
Female 55-day-old Sprague-Dawley rats were treated with a single intravenous dose of 7,12-dimethylbenzanthracene (DMBA), 2 mg/100g of body weight each. At 60 days of age, the rats were divided into four dietary groups (41–42 rats/group): I,5% corn oil diet fed ad libitum; II, 20% corn oil diet fed ad libitum; III,5% corn oil diet fed 12% less than group I; and IV, 20% corn oil diets fed 12% less than group II. The 5% and 20% corn oil diets were purified semisynthetic diets that were isonutrient on a caloric basis. All animals were housed individually in single cages; food consumption of each animal was computed daily throughout the study. Sixteen weeks after carcinogen treatment, mean numbers of mammary carcinomas per rat (±SE) in groups I, III, and IV were 4.1±0.6, 6.8±0.7, 3.0±0.3, and 4.1±0.5, respectively. Mean weight of mammary carcinomas per rat (g±SE) in groups I, II, III, and IV were 3.5 ± 0.7, 8.0 ± 1.3, 3.0± 1.1, and 4.6 ± 1.3, respectively. Mammary carcinoma number and weight were significantly (P<.01) increased in the animals fed the 20% corn oil diet ad libuitum when compared with those fed the 5% corn oil diet ad libitum; however, no significant differences in mammary tumor number or weight were observed between the animals fed a restricted, 20% corn oil diet and those fed a restricted, 5% corn oil diet. The study involving the animals fed the 12%-restricted diets was repeated (38– rats/group), with virtually indentical results, i.e., the mean number of mammary carcinomas per rat in the groups fed the restricted 5% fat and 20% fat diets at termination of the study was 3.1 ± 0.4 and 3.7 ± 0.3, respectively, and the mean weight (g) of mammary carcinomas per rat was 4.3 ± 1.2 and 4.0 ± 1.1, respectively (no significant differences). Thus, high levels of dietary fat can significantly enhance mammary carcinogenesis in female rats, but only in animals on an libitum feeding protocol. A slight restriction in amount consumed (12% less than ad libitum) abolished the mammary carcinogenic differential between a high-fat and a low-fat diet.

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