CHEMOPREVENTION BY MELATONIN AND COMBINED MELATONIN TAMOXIFEN THERAPYOF 2ND-GENERATION NITROSO-METHYLUREA-INDUCED MAMMARY-TUMORS IN RATS

Melatonin, an indole of pineal origin, is known to have an oncostatic effect on carcinogen-induced rat mammary tumours. We have assessed for the first time, the efficacy of melatonin alone and in combination wi th a sub-optimal dose of tamoxifen, a partial oestrogen antagonist, on N-nitroso-N-methylurea-induced rat mammary tumours, Both these agents were administered to Sprague-Dawley rats following excision of the pr imary tumours. Melatonin (200 mu g/day/rat) at the given dose level co uld significantly suppress the appearance of second generation mammary tumours and the latency period of tumour appearance was also signific antly increased (P < 0.001) as compared to vehicle-treated animals, Ta moxifen (60 mu g/week/rat) does not suppress the development of second generation mammary tumours, Go-administration of melatonin and low do se of tamoxifen had no additive or synergistic effect on the preventio n of second generation of mammary tumours, The results warrant the cli nical evaluation of melatonin for chemoprevention and adjuvant therapy .