Diet, overfeeding, and moderate dietary restriction in control Sprague-Dawley rats: I. Effects on spontaneous neoplasms.
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.(ABSTRACT TRUNCATED AT 400 WORDS)
Keenan
K P
KP
Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Soper
K A
KA
Smith
P F
PF
Ballam
G C
GC
Clark
R L
RL
D000821:Animal Feed / Q000009:adverse effects; D000818:Animals; D002423:Cause of Death; D004032:Diet / Q000009:adverse effects*; D005260:Female; D005508:Food Deprivation / Q000502:physiology; D006963:Hyperphagia / Q000503:physiopathology*; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000401:mortality / Q000473:pathology / Q000662:veterinary*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic