Diet, Overfeeding, and Moderate Dietary Restriction in Control Sprague-Dawley Rats: I. Effects on Spontaneous Neoplasms

Abstract

This study was designed to compare the effects of ad libitum (AL) overfeeding and moderate dietary restriction (DR) of two different diets on Sprague-Dawley (SD) rat 2-yr survival and the development of spontaneous neoplasms. SD rats were fed Purina Rodent Chow 5002 or a modified Rodent Chow 5002-9 containing lower protein, fat, metabolizable energy and increased fiber by AL or by DR at 65% of the AL amount by measurement or time (6.5 hr). At 106 wk, rats fed the 5002-9 diet AL did not have significantly improved survival over rats fed the 5002 diet AL. The 5002 diet fed DR by time (6.5 hr) improved survival for males but not females. Only DR by measurement of both diets resulted in lower mortality for both sexes. The most common cause of death in rats of both sexes fed either diet AL was pituitary tumors followed by mammary gland tumors in females and renal and cardiovascular disease in males. The overall tumor incidence by 106 wk was remarkably similar between AL and DR groups. However, compared to the 5002 AL group, a decrease in the age-adjusted (Peto analysis) incidence of pituitary adenoma was observed in all other male groups. This effect was noted in the female DR by measurement groups only. For males, compared to the 5002 AL group, a decrease in the age-adjusted incidence of pancreatic islet carcinoma was observed in the DR by measurement groups only. In females, compared to the 5002 AL group, the only other difference in tumor incidence was the mammary gland tumors, which showed a significant decrease in the age-adjusted tumor incidence or multiplicity in the 5002-9 AL, 5002-9 DR, and 5002 DR groups. Additional analyses of mammary gland tumors showed growth time (time from initial palpation until death), tumor doubling time, and tumor volume were generally not statistically significantly different between AL and DR groups, although AL females could sustain larger tumor volumes. Compared to the 5002 AL group, there were no other significant differences in the age-adjusted incidence of any other tumor site in animals fed a modified diet or subjected to moderate DR of either diet. The conclusion from this study is that moderate DR delays death due to fatal cardiovascular or renal degenerative disease and spontaneous tumors, particularly those of the pituitary and mammary gland. However, moderate DR appears only to delay the time of onset, but not the progression, of these spontaneous tumors whether measured by age-adjusted incidence, growth time, tumor doubling time, or the time between initial detection and death.

Social isolation dysregulates endocrine and behavioral stress while increasing malignant burden of spontaneous mammary tumors

“…Prior to the current study, widely documented as the greatest environmental modulator of mammary tumor development in rodents (26). By comparison, unlimited access to high metabolizable energy food increased tumor incidence by only 90%, produced a modest 1.33 relative risk for malignancy, and had no effect on tumor growth (27).…”

Spontaneous Neoplastic Lesions in Aged Sprague-Dawley Rats.

“…In the subcutaneous tissue, benign lipoma and fibroma as well as malignant fibrosarcoma and malignant fibrous histiocytoma were seen. In the female mammary gland, ports [1,4,5,[8][9][10][11][12][13].…”

Diet, Overfeeding, and Moderate Dietary Restriction in Control Sprague-Dawley Rats: II. Effects on Age-Related Proliferative and Degenerative Lesions

“…In a companion paper we report that moderate dietary restriction (DR) improves SD rat survival and delays death from spontaneous degenerative disease and tumors of the pituitary and mammary gland (27). Moderate DR has this action on these endocrine-related tumors by delaying the time of onset, but not the progression of these tumors when measured by age-adjusted incidence, growth time, doubling time, or time between initial detection and death (27).…”

“…The decline in survival questions the adequacy of exposure of rats to the test article in carcinogenicity studies that result in less than 50% survival at the end of the 2-yr period (4,23,32). We have observed a significant correlation between average daily food consumption and 2-yr survival in 58 control groups of ad libitum (AL) fed SD rats (25)(26)(27). While both genetic and environmental factors are involved, rat survival can be improved by simple dietary restriction (9, 10, 25-27, 38, 39, 41, 42, 56, 57, 72, 73).…”