1. In order to assay the effects of dietary fat on mammary cancer development under conditions of rigidly controlled caloric intake, 84 A × C Line 9935 female rats, with cholesterol pellets containing 4 to 6 mg. of dietylstilbestrol implanted in their scapular region, were distributed into 6 groups and placed on iso-caloric synthetic rations of varying fat and carbohydrate composition.

  2. Diets adequate in protein, minerals, and vitamins, but varying in fat content from 6.5 per cent to 46 per cent Crisco with sufficient dextrin to equalize the caloric content were fed ad libitum and restricted to rats in individual cages.

  3. The caloric intake varied from 40 calories daily for rats on the ad libitum high-fat diet to 34 calories daily for those on the ad libitum low-fat diet and their paired mates on the high-fat diet, and was restricted to 25 calories daily in isocaloric portions of the high-fat, modified low-fat, and low-fat diet in three additional groups.

  4. Restricting the intake to 25 calories daily permitted the rats to live well beyond the average survival periods of the rats on ad libitum rations, but the restricted animals lost considerable weight, were irritable and constantly in search of food.

  5. Restricting the intake to 22 calories per day resulted in the deaths of the majority of the rats within 60 days.

  6. Sixty-seven rats survived for at least 180 days, the approximate minimum latent period for diethylstilbestrol-induced mammary cancer in this strain, and of these, 58 or 87 per cent developed multiple mammary cancers.

  7. Restricting the caloric intake to 74 per cent of the ad libitum consumption did not significantly decrease the percentage of rats that eventually developed mammary cancer, but increased the average latent period from approximately 300 days to 400 days.

  8. A comparison of the paired mates on isocaloric high-fat and low-fat diets showed that more tumors were observed, and the average latent period was somewhat shorter in the rats on the high-fat diet than in their mates on the low-fat diet.

  9. When the high-fat diet was restricted to 25 calories daily, or fed ad libitum at an average consumption of 40 calories daily, neither the number of tumors induced nor the latent periods differed significantly from those on ad libitum low-fat diets.

  10. The only consistent effect of the high-fat diet appeared to be an acceleration of the growth rate of the induced tumors.

  11. Extensive hypertrophy and evidence of an increased secretory activity were consistent histologic features of the mammary gland of the rats on the high-fat diet, although no evidences of hormone insufficiency were observed in the mammary glands of the rats on low-fat or restricted diets.

  12. All 236 gross tumors of the mammary glands and 337 additional microscopic foci were characterized as adenocarcinomas. All of the tumors were generally similar in structure, but the developmental changes appeared more abrupt in the tumors of the rats on the high-fat diet.

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Supported in part by a grant-in-aid from the United States Public Health Service.

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©1949 American Association for Cancer Research.
1949
Cancer Research, Inc.