Chemoprevention by melatonin and combined melatonin-tamoxifen therapy of second generation nitroso-methylurea-induced mammary tumours 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 with 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 primary tumours. Melatonin (200 micrograms/day/rat) at the given dose level could significantly suppress the appearance of second generation mammary tumours and the latency period of tumour appearance was also significantly increased (P < 0.001) as compared to vehicle-treated animals. Tamoxifen (60 micrograms/week/rat) does not suppress the development of second generation mammary tumours. Co-administration of melatonin and low dose of tamoxifen had no additive or synergistic effect on the prevention of second generation of mammary tumours. The results warrant the clinical evaluation of melatonin for chemoprevention and adjuvant therapy.
Kothari
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Cell Biology Division, Tata Memorial Centre, Bombay, India.
Borges
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Kothari
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002273:Carcinogens / Q000009:adverse effects*; D018890:Chemoprevention; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000008:administration & dosage*; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control* / Q000601:surgery; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008770:Methylnitrosourea / Q000009:adverse effects*; D016609:Neoplasms, Second Primary / Q000517:prevention & control*; D014677:Pharmaceutical Vehicles; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage*
D016588:Anticarcinogenic Agents; D018931:Antineoplastic Agents, Hormonal; D002273:Carcinogens; D004965:Estrogen Antagonists; D014677:Pharmaceutical Vehicles; D013629:Tamoxifen; D008770:Methylnitrosourea; D008550:Melatonin