Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague-Dawley rat.
BACKGROUND
It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague-Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented.


METHODS
The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA.


RESULTS
The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation.


CONCLUSIONS
In view of the present results, obtained in the female Sprague-Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors.
Laboratoire de Neuroendocrinologie, CNRS-FRE2718, UFR Biomédicale des Saints-Pères, Université René Descartes, Paris, France. veronique.lenoir@univ-paris5.fr
Véronique
V
Lenoir
Marianne Beau Yon
MB
de Jonage-Canonico
Marie-Hélène
MH
Perrin
Antoine
A
Martin
Robert
R
Scholler
Bernard
B
Kerdelhué
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000230:Adenocarcinoma / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000502:physiology*; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004249:DNA Damage; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000209:etiology / Q000517:prevention & control*; D008550:Melatonin / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors
D000975:Antioxidants; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D008550:Melatonin