Abstract 594: Effect of caloric restriction and high fat diet on azoxymethane-induced carcinogenesis in LETO and OLETF rats

Abstract

Abstract We showed recently that diabetic and mildly obese Otsuka Long-Evans Tokushima Fatty (OLETF) rats are more susceptible to azoxymethane (AOM)-induced Zymbal gland and intestinal carcinogenesis than control Long-Evans Tokushima Otsuka (LETO) rats. In the present study, we examined the effect of caloric restriction (CR) and high-fat diet (HFD) on AOM-induced carcinogenesis in these strains. Experiment 1: Six-week-old male LETO and OLETF rats (n=21) were given s.c. injections of 15 mg/kg AOM once weekly for 3 weeks, then fed, Group 1) control diet, Group 2) 20% CR diet, or Group 3) HFD (control diet with 10% safflower oil), and killed at 36 weeks of age. In LETO rats, the incidences of colon tumors (adenoma plus adenocarcinoma) in Groups 1-3 were 45%, 33% and 55%, respectively. Average number of tumors/rat in CR group was fewer than that in HFD group (P<0.05). In OLETF rats, the incidences of colon tumors in Groups 1-3 were 76%, 48% and 62%, respectively. Zymbal gland tumors in CR group developed later than those in control and HFD groups in OLETF rats. Experiment 2: Male LETO and OLETF rats (n=5) were fed control diet, 20% CR diet or HFD for 5 weeks, and killed at 24 weeks of age. In LETO rats, serum triglyceride, total cholesterol, insulin and leptin levels decreased by 20% CR, and increased by HFD compared to the control group. In OLETF rats, those levels decreased by 20% CR, and increased by HFD except leptin. Expression of hepatic IGF-1 and Sirt-1 mRNA elevated by 20% CR in both strains. The liver of OLETF rat HFD group showed severe fatty change histologically. In conclusion, 20% CR inhibited, and HFD promoted colon carcinogenesis in LETO rats. In OLETF rats, 20% CR inhibited, but HFD did not promote colon carcinogenesis because of early development of Zymbal gland tumors. Hyperinsulinemia and/or hyperlipidemia may exert the promoting effect in rat carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 594. doi:1538-7445.AM2012-594