Inhibitory effect of melatonin on 7,12-dimethylbenz[a]anthracene-induced carcinogenesis of the uterine cervix and vagina in mice and mutagenesis in vitro

Forty female CBA mice aged 3-4 months were exposed twice a week during 2 mo nths to intravaginal applications of polyurethane sponges impregnated with 0.1% solution of 7,1 2-dimethylbenz[a]anthracene (DMBA) in triethyleneglyco l. Three hours after each application the sponges were taken out. Starting from the day of the Ist DMBA application a part of mice was exposed five ti mes a week during 4 months with melatonin in tap water (20 mg/l) given at n ight time (from 18:00 to 09:00 h). Additional 20 female CBA mice were intac t and served as a control. All mice were sacrificed in 6 months after start of the experiment. Seven of 20 mice exposed to DMBA alone developed malign ancies in the vagina and cervix uteri and two mice developed benign cervica l tumors. No malignancies in vagina and uterine cervix and three vaginal pa pillomas were observed in mice exposed to DMBA + melatonin. There were no a ny tumors in intact controls. Two in vitro tests were used for mutagenicity studies: the Ames test (strains TA 97 and TA 98 of Salmonella typhimurium) and the single cell gel electrophoresis assay (SCGE assay or COMET assay) performed on CHOK1 cells. In tested strains melatonin significantly reduced the mutagenicity of DMBA. In the SCGE assay preincubation with melatonin l ed to a strong inhibition of clastogenic activities of DMBA. Thus, our data indicate that pineal indole hormone melatonin inhibits cervical and vagina l carcinogenesis induced by DMBA in mice and possess antimutagenic and anti clastogenic effect in vitro. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.