© 1992 Oxford University Press
research-article |
Effects of Diet Type on Incidence of Spontaneous and 2-Acetylaminofluorene-Induced Liver and Bladder Tumors in BALB/c Mice Fed AIN-76A Diet versus NIH-07 Diet
*National Center for Toxicological Research Jefferson, Arkansas 72079
Pathology Associates, Inc., NCTR Jefferson, Arkansas 72079
Received January 4, 1991; accepted August 30, 1991
Diet is a major influence on the responses of experimental animals to drugs, toxins, and carcinogens. Two diets used widely in toxicological and/or nutritional studies, and considered to be nutritionally adequate, were compared with respect to their influence on growth, body weight, lifespan, spontaneous neoplasia, and neoplastic responses to 2-acetylaminofluorene (2-AAF). Both sexes of weanling BALB/c mice were fed either a purified diet (AIN-76A) or a nonpunfied, natural ingredient diet (NIH-07), with or without 2-AAF for up to 2 years. Dosages of 2-AAF were administered to males at 0, 20, 40, or 60 ppm in each diet and to females at 0, 100, 125, or 150 ppm. Each group consisted of 96 mice. In most instances, males and females fed purified diet (AIN-fed) gained weight more rapidly, attained higher maximum body weights, and died earlier than their non-purified diet (NIH-fed) counterparts. 2-AAF inhibited weight gain significantly only in AIN-fed females. Thus, females receiving 150 ppm 2-AAF gained little more than their NIH-fed counterparts. At the dosages used in males, 2-AAF did not induce liver neoplasia but the AIN diet was clearly associated with a higher spontaneous frequency of liver neoplasia than the NIH diet. Although 2-AAF induced liver tumors in females fed either diet at all dosages, a higher frequency and earlier appearance of liver tumors among AIN-fed females than their NIH-fed counterparts was apparent mainly at the lowest dosage. 2-AAF induced bladder neoplasia in both sexes. AIN-fed males were much more sensitive to this effect than NIH-fed animals; however, diet had no impact on the induction of bladder neoplasia in females. This study dramatically shows the importance of diet selection on the outcome of carcinogenicity studies. However, the results suggest that dietary differences may not be consistently found among different sexes or strains and that differences between purified and nonpurified diets in the carcinogenic response to a carcinogen may be related to their differential effects on body weight.