Preventive effects of raloxifene and melatonin in N-methyl-N-nitrosourea-induced mammary carcinogenesis in female rats

The aim of this study was to evaluate preventive effects of raloxifene (RAL), melatonin (MEL) and their combination in N-methyl-N-nitrosourea (NMU)-induced rat mammary carcinogenesis. MEL-treatment began 12 days and RAL treatment began 10 days prior to carcinogen administration and continued till the end of experiment (24 weeks after first carcinogen administration). RAL was administered subcutaneously twice a week in the dose of 5mg/kg b.w. MEL was administered diluted in drinking water in a concentration 4 mug/ml daily from 3 p.m. to 8 a.m. At the end of experiment, tumor incidence, frequency, latency period and tumor volume as parameters of mammary carcinogenesis were evaluated. Moreover, the effect of chemopreventives on body and uterine weight, food and water intake were recorded. In RAL-treated group, tumor incidence was decreased by 67% (p < 0.001), tumor frequency per group was reduced by 90% (p < 0.0002) and latency period lengthened by 27 days in comparison with control group. After MEL-treatment tumor incidence was decreased by 19%, tumor frequency per group was decreased by 50% (p < 0.05) when compared to control animals. The effect of RAL+MEL-treatment was very similar to that of RAL-treatment. In groups with RAL administration, significant decrease (p < 0.0001) in body weight gain and relative uterine weight was recorded. As to food intake no significant differences in comparison with control group were found. Consequently, groups were pooled and in RAL-treated groups (RAL, RAL+MEL) a decrease in food intake, when compared to groups without RAL administration (control group, MEL) was recorded (p < 0.04). The water intake was markedly decreased in RAL-treated groups (p < 0.0001). RAL and RAL+MEL proved to be very effective in prevention of experimental mammary carcinogenesis in female rats, isolated MEL appeared to be of lower oncostatic activity.