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Influence of Protein Under- and Overnutrition on Spontaneous Tumor Prevalence in the Rat¹

The Institute for Cancer Research, Fox Chase, Philadelphia, Pennsylvania 19111 and Pathologic Institute, Faculty of Medicine, University of Utrecht, The Netherlands

The protein/calorie ratio of the diet under ad libitum and restricted isocaloric conditions of feeding has been found to modify the risk of incurring spontaneous tumors in the male rat. The direction and magnitude of the influence, which differed with the mode of feeding, were dependent on the tissue origin, type and malignancy of the tumor. Under ad libitum feeding conditions, chronic marginal protein undernutrition predisposed the rats to an early occurrence and high morbidity of tumors of lymphoreticular and hematopoietic tissues, particularly the thymus. Protein over-nutrition, in contrast, increased the susceptibility to urinary bladder papillomas. For other types of tumors of epithelial origin, principally those occurring in the pituitary, thyroid and pancreas, the highest morbidities were obtained when the rats were fed a diet adequate in protein content. The morbidities of these tumors were markedly decreased when the level of protein was either marginally low or excessively high. Tumors of connective tissue were little affected. Under restricted feeding conditions, malignant epithelial tumor risk increased with the degree of protein deprivation. The risk of reticulum cell sarcomas was also low when the diet was high in protein. Although the morbidity of tumors of the thyroid gland was inversely related to the proportion of protein, for tumors of the parathyroid gland it was directly related. Adrenal tumor morbidity was lowest when the diet was high in protein. The influence of the level of dietary protein on tumors of the pituitary, pancreas, thymus and lung could not be assessed since such tumors occurred infrequently among underfed rats.

KEY WORDS: • protein deficiency • protein excess • undernutrition • tumors • malignancy • incidence • morbidity • aging • longevity

¹ Supported by U. S. Public Health Service grants HD-00086, HD-00490, CA-06927 and RR-05539, and by an appropriation from the Commonwealth of Pennsylvania.

Manuscript received 6 November 1972.

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