Effects of Dietary Protein, Fat and Energy Intake during an Initiation Phase Study of 7,12-Dimethylbenz[a]anthracene-lnduced Breast Cancer in Rats12 STEVEN K. CLINTON,3' JOAN M. ALSTER,t PETER B. IMREY,T STEVEN NANDKUMAR,Õ C. RICHARD TRUEX* ANDWILLARD J. VISEK4* 'Nutrition and Metabolism, ^Medical Statistics and Epidemiology, and ÎPathology, University of Illinois College of Medicine, Urbana, IL 61801 ABSTRACT A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of en ergy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)- induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen adminis tration all rats consumed a diet containing 16 % of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85 % with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32 % of energy prior to DMBA were prevalences of 79, 65 and 59 % , with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a signifi cant reduction in tumor prevalence, which was most striking between 8 and 16 % of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the in itiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis. J. Nutr. 116: 2290-2302, 1986. INDEXING KEY WORDS dietary fat •corn oil •dietary protein •casein • caloric intake •7,12-dimethylbenz[a]anthracene •breast cancer •rats Soon after the development of experimen- tal models for carcinogenesis it became ap- »IZATelAÕ»^' W«* parent that tumor development involved at 'This research was supported by National Cancer Institute of the Na- least two ctens rprn<mÕ7pHas initiation and tionalInstitutes °f HealthGrant Nos CA29629 andCA23326 andEn- leaSI TWO „OgniZea aS I vironmental Toxicology Training Grant No. USPHS-ES 070001-17. promotion (1-4). Although it ¡S increasingly 'A preliminary report of this research was presented at the 65th Annual evident that cancer development is an evo- ££SÄ ""m. ÄÄ^Ä multiStep prOCeSS (5, 6) involving mar. S- Imrey- v- B & Visek. W J- <1981> Dietary protein-fat mterac- v ' -- f , , i . . , , lions in the initiation and promotion of 7,12-dimenthylbenz[a]- Series Ot Changes at the blOChemiCal, Cel- anthracene (DMBA) mammary cancer. Fed. Proc. 40:948 (abst. 4071). and SVStemiC levels, the Original tWO- 'Present address: The University of Chicago, Department of Medicine, 1^_ _ 950 East 59th Street, Chicago, IL 60637. Stage model Of CarCinOgeneSIS remains a 'To whom requests for reprints should be addressed. 2290 by guest on July 10, 2011 jn.nutrition.org Downloaded from