Document Detail


The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins.
MedLine Citation:
PMID:  20401468     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene, ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium, lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic, glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1 retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary and key role in determination the selective response of Ty1 test to carcinogenic genotoxins.
Authors:
Martin Dimitrov; Pencho Venkov; Margarita Pesheva
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-17
Journal Detail:
Title:  Archives of toxicology     Volume:  85     ISSN:  1432-0738     ISO Abbreviation:  Arch. Toxicol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0417615     Medline TA:  Arch Toxicol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  67-74     Citation Subset:  IM    
Affiliation:
Sofia University, Bulgaria.
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