Melatonin and retinyl acetate as chemopreventives in DMBA-induced mammary carcinogenesis in female Sprague-Dawley rats.

One goal of experimental oncology is to find and test effective chemopreventive substances which can suppress malignant transformation of the cells, their accumulation and invasion. Mammary gland tumours were induced by DMBA applied intragastrically (10 mg/rat, three times) every three days between postnatal days 50 and 60 in female Sprague-Dawley rats. One day after the last dose we started chemoprevention with Mel, RA and combination of both drugs, which lasted 25 weeks. Mel was drunk continuously as a solution in tap water (100 micrograms/ml). RA was applied daily in the dose of 8.2 mg/rat at the base of the tongue. There were four experimental groups: 1. control--no chemoprevention, 2. Mel treatment, 3. RA treatment, 4. application RA + Mel. At the end of the experiment the incidence, frequency, latency and average volume of tumours were evaluated. In the group treated with Mel tumour incidence, latency and volume did not differ from controls; the frequency of tumours was decreased. Treatment with RA and with combination RA + Mel decreased mammary tumour incidence to 38% (RA) and 48% (RA + Mel); it also decreased frequency and prolonged latency. Thus chemoprotective effects of RA and combination of RA with Mel were proved in mammary carcinogenesis induced by DMBA. The oncostatic effect of Mel alone was not confirmed. In our recent paper (Bojková et al., 2000) drinking of lower doses of Mel during the late afternoon and night prolonged the latency period and in combination with RA showed an oncostatic effect on mammary carcinogenesis induced by NMU. Further studies are needed to elucidate the conditions of successful chemoprevention with Mel.