A. Kothari et al., COMBINATION OF MELATONIN AND TAMOXIFEN AS A CHEMOPROPHYLAXIS AGAINST N-NITROSO-N-METHYLUREA-INDUCED RAT MAMMARY-TUMORS, Cancer letters, 111(1-2), 1997, pp. 59-66
The effect of melatonin (Mel) and or tamoxifen (Tam) was evaluated on
a mammary tumor model induced in 50 day old female Sprague-Dawley rats
by a single intraperitoneal (i.p.) injection of a direct carcinogen,
N-nitroso-N-methylurea (NMU) (50 mg/kg b.wt./rat). These animals were
treated with either Mel 200 mu g/rat per day, orally in drinking water
and/or Tam (s.c.) 60 mu g/rat per week or 180 mu g/rat per week. The
total observation period was 300 days post-NMU administration in all t
he animals. The mean latency period of tumor appearance and tumor inci
dence was recorded. The mean latency period was significantly lengthen
ed in all the treated groups as compared to that in the only NMU-admin
istered rats (P < 0.001). Highly significant suppression of tumor inci
dence was observed in Mel + Tam(180) group (P < 0.001). The other two
groups i.e. Mel + Tam(60), and Tam(180) also showed significant suppre
ssion of tumor incidence (P < 0.01). Eight weeks after the initiation
of treatment regimen, we observed marked reduction in [H-3]thymidine i
ncorporation into mammary gland DNA of Mel- and/or Tam-treated groups
of animals as compared to the age-matched controls and NMU-administere
d rats, which correlated positively with the sparse mammary gland deve
lopment seen in the whole mount preparations. The result of the combin
ed therapy is highly promising and warrants clinical evaluation in the
prophylaxis of breast carcinogenesis in humans. (C) 1997 Elsevier Sci
ence Ireland Ltd.