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Inhibition of Skin Tumor Promotion by Restriction of Fat and Carbohydrate Calories in SENCAR Mice¹

Eppley Institute for Research in Cancer [D. F. B., H. J. P., T. B., A. P., K. D.] and Department of Biochemistry and Molecular Biology [D. F. B.], University of Nebraska Medical Center, Omaha, Nebraska 68198-6805

The purpose of this research was to compare the influence of calorie restriction by removal of fat with calorie restriction by removal of carbohydrate on the promotion of skin tumorigenesis in mice. Female SENCAR mice were initiated with 7,12-dimethylbenz(a)anthracene (10 nmol, single topical treatment) and fed calorie-restricted diets during and following promotion with 12-O-tetradecanoylphorbol-13-acetate (2 µg, topically, twice a week for 20 weeks). Control diet (American Institute of Nutrition-based formulation) was compared with a diet in which calories from fat and calories from carbohydrate were similar [balanced high fat (BHF)] in ad libitum-fed groups. Restricted animals were fed diets such that 35% of the calories from fat [high carbohydrate, calories restricted from fat (HCR)] or from carbohydrate (high fat, calories restricted from carbohydrate) were restricted, but other intake was equivalent to the BHF group. Results showed an inhibition of papilloma number in both restricted groups and the inhibition was greatest in the HCR mice. Larger papillomas were observed on mice in the control, BHF, and high-fat, calories restricted from carbohydrate diet groups than on mice in the HCR group. The pattern of carcinoma development was similar in the mice in the freely fed control and BHF groups. Restriction of calories from either fat or carbohydrate delayed the rate and reduced the incidence of carcinoma development. Carcinoma incidence did not differ between mice fed the high-fat, calories restricted from carbohydrate and HCR diets.

¹ Supported by NIH Grant R01 CA4986, NIH Core Grant CA36727, and American Cancer Society Grant SIG-16.

² To whom requests for reprints should be addressed, at Eppley Institute, University of Nebraska Medical Center, 600 South 42nd Street, Omaha, NE 68198-6805.

Received 6/11/92. Accepted 10/21/92.

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