Effects of tamoxifen and melatonin on mammary gland cancer induced by N-methyl-N-nitrosourea and by 7,12-dimethylbenz(a)anthracene, respectively, in female Sprague-Dawley rats.
Chemopreventive effects were analysed of antioestrogen TAM and of MEL on NMU- or DMBA-induced mammary gland cancer, respectively, in female Sprague-Dawley rats. NMU was administered intraperitoneally in two doses each of 50 mg/kg b.w. between 46th-57th postnatal days. DMBA was given by gavage in one dose (20 mg per animal) between 50th-54th postnatal days. The treatment with MEL began 12 days and the treatment with TAM 10 days before carcinogen administration; both chemopreventive substances were administered until the end of the experiment (24 weeks after carcinogen application). TAM was administered subcutaneously twice a week in a dose 2.5 mg/kg b.w. MEL was given in tap water (20 mg/ml) daily between 3 p.m. to 8 a. m. The tumour incidence, tumour frequency per group and animal, latency period, tumour volume, body weight gain in the rats and weight of uterus (in the experiment with NMU) were evaluated. TAM suppressed carcinogenesis to 0% incidence like TAM+MEL in both the NMU and DMBA models. In NMU-induced mammary carcinogenesis MEL lowered the tumour volume (although statistically non-significantly) by 30% in comparison with the control group; in DMBA-induced mammary carcinogenesis it lowered the tumour volume (2.70 +/- 0.81 cm3 vs. 0.90 +/- 0.33 cm3) and lengthened (non-significantly) the latency period (by 12 days). The weight gain of animals in both NMU and DMBA models and relative uterus weight in the NMU model were significantly lower in the groups treated with TAM and TAM+MEL as compared to the control group and the group treated with MEL. Evaluation of the combined effect of TAM+MEL was not possible due to total suppression of carcinogenesis by TAM. TAM and TAM+MEL are highly effective agents in rat mammary carcinogenesis prevention, but the side effects of TAM in humans limits its use in clinical oncology.
Institute of Animal Physiology, Faculty of Science, P.J. Safárik University, Kosice, Slovakia.
P
P
Kubatka
B
B
Bojková
K
K
M ciková-Kalická
M
M
Mníchová-Chamilová
E
E
Adámeková
I
I
Ahlers
E
E
Ahlersová
M
M
Cermáková
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000517:prevention & control*; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D008770:Methylnitrosourea / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage / Q000494:pharmacology*
D002273:Carcinogens; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; D008550:Melatonin