title: Neoplastic pathology in male Sprague-Dawley rats fed AIN-93M diet ad libitum or at restricted intakes.
abstract: The primary purpose of this study was to evaluate the effects of age and long-term dietary reduction on neoplastic diseases in rats fed the AIN-93M purified diet. Second, pathologic profiles are critical to comprehensive dietary evaluation. Male Sprague-Dawley rats assigned to 2 groups, ad libitum (AL) and dietary restricted (DR), were fed the AIN-93M (casein protein) diet free choice and reduced in amount by 31%, respectively. At 58 weeks of age, the predominant types of lesions in AL and DR rats were pituitary and skin tumors. At 114 weeks of age, the most common lesions were pituitary, adrenal gland, skin, mammary, brain, and pancreatic tumors and mononuclear cell leukemia. However, DR had no significant effect on these lesions. Primary findings demonstrate that DR significantly reduced the total number of tumors per rat and incidence of benign and primary tumors (all organs) but did not reduce the incidence of malignant tumors (all organs). Dietary restriction increased the percentage of unknown deaths. These results may explain why survival rates for AL and DR rats were not significantly different at 114 weeks (43.3 vs 57.5%, respectively). These findings differ from previous studies using NIH-31 cereal diet (Aging Clin Exp Res 2001;13:263; J Nutr 2002;132:101; Aging Clin Exp Res 2003;16(6):68; Aging Clin Exp Res 2004;16:448) where neoplastic lesions rather than nonneoplastic lesions were linked to a significant increase in survival rate among cohorts of DR-fed rats (J Nutr 2002;132:101). Factors such as diet composition and digestibility, although not independent of body weight, may have contributed to differences in rat mortality and may affect humans in a similar manner.
authors.affiliation: Division of Genetic and Reproductive Toxicology, National Center for Toxicological Research, FDA, Jefferson, AR 72079, USA. peter.duffy@fda.hhs.gov
authors.forename: Peter H
authors.initials: PH
authors.lastname: Duffy
authors.forename: Sherry M
authors.initials: SM
authors.lastname: Lewis
authors.forename: Martha A
authors.initials: MA
authors.lastname: Mayhugh
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Trotter
authors.forename: Bruce S
authors.initials: BS
authors.lastname: Hass
authors.forename: John R
authors.initials: JR
authors.lastname: Latendresse
authors.forename: Brett T
authors.initials: BT
authors.lastname: Thorn
authors.forename: Graham
authors.initials: G
authors.lastname: Tobin
authors.forename: Ritchie J
authors.initials: RJ
authors.lastname: Feuers
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D031204:Caloric Restriction; D002364:Caseins / Q000008:administration & dosage*; D004044:Dietary Proteins / Q000008:administration & dosage*; D015994:Incidence; D008136:Longevity / Q000502:physiology; D008297:Male; D009369:Neoplasms / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D002364:Caseins; D004044:Dietary Proteins