Document Detail


Endogenous sex hormones affect the mutagen-induced chromosome damage by altering a caffeine-sensitive checkpoint.
MedLine Citation:
PMID:  15708586     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the present study we analysed the effect of endogenous sex hormones on the SCE frequencies induced in vitro by mitomycin C (MMC), a bifunctional alkylating agent producing high chromosome damage and mitotic arrest. The analysis has been performed on lymphocytes obtained at three different phases of menstrual cycle, from women with regular cycle and hormones dosage. At all phases we further analysed the effect of a post-treatment with caffeine, an agent that it is known to overrride the DNA damage checkpoints. After MMC, the cultures obtained at ovulation and luteal phases have SCE frequencies statistically higher than the cultures obtained at the progestogenic phase, showing increases of 15 and 25%, respectively. After caffeine, the MMC treated cultures which were set up at the progestogenic phase show a high potentiation of SCE frequencies (28%) whereas the treated cultures set up at ovulatory and luteal phases show little or no potentiation. These findings demonstrate that the endogenous hormones greatly modulate the SCE frequencies induced by the mutagen; they also indicate that hormones action competes with the caffeine effect. Caffeine acts by abrogating the mitotic arrest produced by DNA damage and induced cells with a higher chromosome damage into a premature mitosis. Our findings suggest that endogenous hormones could overcome the checkpoint controls activated in cells after mutagenic exposure. This action may be an epigenetic mechanism relevant in hormone carcinogenesis.
Authors:
Leonardo Cocchi; Vittoria Scarcelli; Aldamaria Puliti; Roberto Barale; Isabella Sbrana
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Mutation research     Volume:  570     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-14     Completed Date:  2005-04-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  281-8     Citation Subset:  IM    
Affiliation:
Department of Human and Environmental Sciences, University of Pisa, Vian San Guiseppe 22, Pisa 56126, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adult
Caffeine / pharmacology*
Female
Gonadal Steroid Hormones / physiology*
Humans
Mutagens / toxicity*
Sister Chromatid Exchange
Chemical
Reg. No./Substance:
0/Gonadal Steroid Hormones; 0/Mutagens; 58-08-2/Caffeine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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