Keenan K P, Soper K A, Smith P F, Ballam G C, Clark R L
Department of Safety Assessment, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Toxicol Pathol. 1995 May-Jun;23(3):269-86. doi: 10.1177/019262339502300305.
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)
本研究旨在比较随意过量喂食（AL）和适度饮食限制（DR）两种不同饮食对斯普拉格-道利（SD）大鼠2年生存率及自发性肿瘤发生的影响。SD大鼠通过AL或按测量值或时间（6.5小时）以AL量的65%进行DR，喂食普瑞纳啮齿动物饲料5002或改良的啮齿动物饲料5002-9，后者蛋白质、脂肪、可代谢能量含量较低且纤维含量增加。在106周时，喂食5002-9饲料AL的大鼠与喂食5002饲料AL的大鼠相比，生存率无显著提高。按时间（6.5小时）对5002饲料进行DR可提高雄性大鼠的生存率，但对雌性大鼠无效。仅通过测量对两种饲料进行DR可降低两性的死亡率。两种饲料AL喂养的大鼠中，两性最常见的死亡原因均为垂体肿瘤，其次雌性为乳腺肿瘤，雄性为肾脏和心血管疾病。到106周时，AL组和DR组的总体肿瘤发生率非常相似。然而，与5002 AL组相比，在所有其他雄性组中观察到垂体腺瘤的年龄调整后（Peto分析）发生率有所下降。仅在按测量值进行DR的雌性组中发现了这种效应。对于雄性大鼠，与5002 AL组相比，仅在按测量值进行DR的组中观察到胰岛癌的年龄调整后发生率有所下降。对于雌性大鼠，与5002 AL组相比，肿瘤发生率的唯一其他差异是乳腺肿瘤，在5002-9 AL、5002-9 DR和5002 DR组中，其年龄调整后肿瘤发生率或肿瘤数量显著下降。对乳腺肿瘤的进一步分析表明，生长时间（从最初触诊到死亡的时间）、肿瘤倍增时间和肿瘤体积在AL组和DR组之间通常无统计学显著差异，尽管AL组雌性大鼠可维持更大的肿瘤体积。与5002 AL组相比，喂食改良饲料或对任何一种饲料进行适度DR的动物在任何其他肿瘤部位的年龄调整后发生率均无其他显著差异。本研究的结论是，适度DR可延迟因致命性心血管或肾脏退行性疾病及自发性肿瘤，特别是垂体和乳腺肿瘤导致的死亡。（摘要截断于400字）
