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

Abstract:

:Forty female CBA mice aged 3-4 months were exposed twice a week during 2 months to intravaginal applications of polyurethane sponges impregnated with 0.1% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in triethyleneglycol. Three hours after each application the sponges were taken out. Starting from the day of the 1st DMBA application a part of mice was exposed five times a week during 4 months with melatonin in tap water (20 mg/l) given at night time (from 18:00 to 09:00 h). Additional 20 female CBA mice were intact 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 malignancies in the vagina and cervix uteri and two mice developed benign cervical tumors. No malignancies in vagina and uterine cervix and three vaginal papillomas were observed in mice exposed to DMBA+melatonin. There were no any 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 led to a strong inhibition of clastogenic activities of DMBA. Thus, our data indicate that pineal indole hormone melatonin inhibits cervical and vaginal carcinogenesis induced by DMBA in mice and possess antimutagenic and anticlastogenic effect in vitro.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Anisimov VN,Zabezhinski MA,Popovich IG,Zaripova EA,Musatov SA,Andre V,Vigreux C,Godard T,Sichel F

doi

10.1016/s0304-3835(00)00463-8

keywords:

subject

Has Abstract

pub_date

2000-08-11 00:00:00

pages

199-205

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304383500004638

journal_volume

156

pub_type

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