Effects and mechanisms of various calorie restriction methods on experimental carcinoma of sprague dawley rats

Preventive effects of calorie restrictions on age-related chronic diseases are well known. In studies regarding the effects of calorie restriction on cancer, restrictions were started generally at the time of induction or a few days later. Studies where calorie restriction started after the tumor has been developed are rare, and these are restricted to only a few tumor types. This study (model) aimed to investigate the effects of different calorie restrictions, starting after tumor growth progressed to a certain degree, on tumor growth in induced breast cancer models. A total of 34, 21-days old female Sprague Dawley rats were used. Breast cancer was induced via NMU (50 mg/kg/i.p.) on 29 rats. When tumors grow to 10-12 mm, rats were divided into 3 groups paired according to tumor size: animals in one group were given chow diet ad libitum and served as cancer controls (CC), while others undergo to 50% calorie restriction (CR-50%) or fed alternate days (ADF) for following 12 weeks. Other 5 animals were given physiological saline and served as ad libitum-fed healthy controls. Body weights and, once palpable, tumor diameters were recorded weekly. At the end of experiment animals were euthanized, tumors excised, weighed and their diameters measured. Tumor volumes were calculated by their sizes. In sera prepared from blood samples, concentrations of the insulin, IGF-I, corticosterone, leptin and adiponectin were determined via ELISA. Data were analyzed by ANOVA, ANOVA for repeated measures in factor time and Kruskal Wallis test. CR-50% caused rapid weight loss in rats, so that animals lost 26-38% of their initial live weights within 6 weeks, and experiment terminated for this group after 6 weeks. Mean body weight of controls was higher than that of CC, ADF and CR-50%, and mean body weight of CC was higher than that of ADF and CR-50%. However, neither volumes nor weights of tumors differed between groups. Serum insulin, IGF-I, leptin and corticosteron concentrations did not differ between groups. All tumors from %50-CR group excised at the end of 6th week of experiment were benign. Highest incidence of malign and invasive tumors at the end of 12th week was encountered in CC. Key words: Alternate day fasting, breast cancer, calorie restriction, female Sprague Dawley rats, NMU