Response in DNA ploidy of hepatocytes to tamoxifen and/or melatonin in vivo.
Tamoxifen is known to induce hepatocarcinogenesis in experimental animals and reversible chronic liver diseases in humans. Melatonin has been recently introduced as an oncostatic agent, especially for hormone-dependent tumors. This study was designed in order to investigate whether melatonin has an effect onthe tamoxifen-induced hepatotoxicity. Wistar albino rats were injected tamoxifen citrate intraperitoneally in three different doses (10 mg/kg and 20 mg/kg bw for 26 days; and 45 mg/kg bw for three days). Another group of animals were treated with melatonin once a week in addition to daily tamoxifen injections, whereas the third group received melatonin only. The control animals were injected an equal volume of diluent at corresponding intervals. At the end of the experimental period, the animals were sacrificed and the livers were prepared for the flow cytometric DNA analysis. DNA histograms were analyzed using the multicycle program. In experimental groups, all animals had aneuploid cell population. The difference in the diploid/ aneuploid ratio of each experimental group as compared to the control group according to Fischer's exact test was found to be highly significant (p < 0.002 MEL vs control; and p < 0.0001 for both TAM vs control and MEL+TAM vs control). Among the tamoxifen-injected animals, the proportion of multiploidy to aneuploid cell population was 17, similar to those treated solely with melatonin. Although the melatonin plus tamoxifen group had higher multiploidy percentage (38%), the difference was not statistically significant as compared to the tamoxifen (or melatonin) groups. No significant difference was noted between the animals which were treated with three different doses of tamoxifen. S-phase fraction percentage was significantly different in melatonin- and melatonin plus tamoxifen-injected animals with regard to controls, the degree of significancy being < 0.05 for both. According to our data, tamoxifen injections induced DNA aneuploidy, but did not stimulate proliferation in the liver as estimated by S-phase fraction. Melatonin, whether alone or in combination with tamoxifen, stimulated cell proliferation and produced aneuploidy.
Süzme
R
R
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.
Gürdöl
F
F
Deniz
G
G
Ozden
T
T
D000782:Aneuploidy; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000517:prevention & control; D005260:Female; D005434:Flow Cytometry; D008550:Melatonin / Q000627:therapeutic use*; D011003:Ploidies; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000037:antagonists & inhibitors / Q000633:toxicity*
D018931:Antineoplastic Agents, Hormonal; D000975:Antioxidants; D013629:Tamoxifen; D008550:Melatonin