Raloxifene and melatonin in prevention of 7,12-dimethylbenz (a) anthracene-induced mammary carcinogenesis in female rats

The tumour suppressive effects of the selective oestrogen receptor modulator (SERM) raloxifene (RAL), pineal hormone melatonin (MEL) and their combination in prevention of 7, 12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats were evaluated. RAL was administered subcutaneously twice a week at a dose of 5 mg/kg b.w. MEL was administered diluted in drinking water in a concentration of 4 mug/ml daily from 3 p.m. to 8 a.m. Application of RAL started 10 days and MEL 12 days before administration of DMBA and continued until the end of the experiment (24 weeks after carcinogen administration). Incidence, frequency, latency and tumour volume as parameters of mammary carcinogenesis were evaluated. In addition, the effects of chemopreventives on body and uterine weight, food and water intake were recorded. In the RAL-treated group a decrease in tumour incidence by 80% (P < 0.01) and tumour frequency per group by 84% (P < 0.01) was found in comparison with the control group. After MEL treatment tumour incidence was decreased by 39% and tumour frequency per group by 47%. The effect of RAL+MEL caused a decrease in incidence by 91% (P < 0.001), latency period lengthened (one tumour per group) by 7 weeks in comparison with the control group. In the groups with RAL a significant decrease in weight gain (P < 0.0001) and a decrease in the absolute and relative uterine weight (P < 0.0001) was found at the end of the experiment. RAL caused a decreased water intake (P < 0.0001), but food intake was not influenced. RAL and a combination of RAL+MEL proved to be very effective in prevention of DMBA-induced mammary carcinogenesis in female rats. MEL alone displayed a lower oncostatic activity in comparison with raloxifene.