67 Cancer Letters, 68 (1993) 67 - 73 Elsevier Scientific Publishers Ireland Ltd. Effect of restricted caloric intake on the development of the azoxymethane-induced glutathione S-transferase placental form positive hepatocellular foci in male F344 rats Shigeyuki Sugiea, Takuji Tanakaa, Hideki Mori” and Bandaru S. Reddyb zyxwvutsrqponmlkjihgfed ‘%epartment of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Pathology, Gifu University School of zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFE Medicine, 40 Tsukasa-machi, Gifu-City 500 (Japan) and bDiuision of Nutritional Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Dana Road, Valhalla, New York 10595 (USA) (Received 23 October 1992) (Accepted 27 October 1992) Summary zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA The modifying effect of 30% caloric restric- tion on the occurrence of azoxymethane (AOM)-induced glutathione S-transjerase pla- cental form (GST-P) positive hepatocellular foci was investigated in male F344 rats. Start- ing at 5 weeks of age, groups of animals were fed ad libitum a high-jut (23.5%) semipurified diet. At 7 weeks of age, all animals except the vehicle-treated groups were S.C. injected with AOM (15 mg/kg body wt., once weekly for 2 weeks). Four days after the second injection, groups of animals were continued on high-fat diet and fed ad libitum (ad libitum group) whereas other groups were restricted to 70% of total calories (calorie-restricted group) con- sumed by the ad libitum group, but received the same amounts of jiber, vitamins and minerals. Thirty-two weeks after AOM injec- tions, all animals were necropsied and livers were sectioned and stained for GST-P by a im- munohistochemical technique for quantitative analysis of enzyme altered foci of the liver. Comparing AOM treated groups. The density zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGF Correspondence to: S. Sugie, Department of Pathology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu-City 500 Japan. and the unit area of enzyme altered foci were significantly lower in the calorie-restricted group (3.84 * 1.55/cm2, 7.96 * 5.43%) than in the ad libitum group (10.14 f 3.621 cm*, 28.11 f 12.33%). The size of foci was also reduced in the calorie-restricted group (17.15 x 10e3 mm* us. 32.36 x 10e3 mm*). The incidence and density of hepa- tocellular foci in rats fed calorie restricted diet were significantly lower than those in rats fed ad libitum, comparing uehicle-treated groups. These results indicate that calorie restriction inhibited the occurrence of both of spon- taneous and AOM induced GST-P positiue foci in rats. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSR Keywords: restriction; hepatocarcinogene- sis; rat; azoxymethane; GST-P positive foci Introduction The concept of a relationship between caloric intake and carcinogenesis is more than 50 years old [3,7]. The demonstration that overweight or obese men had a higher cancer mortality rate than normal or underweight men led to pioneering studies by Tannenbaum and colleagues which indicated that caloric 0304-3835/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd Printed and Published in Ireland