Inhibitory effects of the pineal hormone melatonin and underfeeding during the promotional phase of 7,12-dimethylbenzanthracene-(DMBA)-induced mammary tumorigenesis.

The effects of melatonin (Mel) and/or underfeeding (30% food restriction) on 7,12-dimethylbenzanthracene (DMBA)-induced mammary tumorigenesis were examined in female Sprague-Dawley rats fed a semipurified diet. During the promotional phase of tumorigenesis, the animals began receiving either daily afternoon Mel (250 micrograms) or saline vehicle injections s.c. for 15 weeks. As compared with fed animals, underfed rats had a lower tumor incidence, tumor number and size while the latency to onset and regression of tumors was increased. Melatonin in fed rats moderately suppressed tumor incidence and number. However, the combination of Mel treatment and underfeeding caused the most marked inhibition of tumorigenesis as compared with either treatment alone. These results indicate that Mel administration and/or underfeeding during the promotional phase inhibit DMBA-induced mammary tumorigenesis perhaps via neuroendocrine and/or peripheral endocrine mechanisms.