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Tags
HERO ID
2149176
Reference Type
Journal Article
Title
Ogg1 genetic background determines the genotoxic potential of environmentally relevant arsenic exposures
Author(s)
Bach, J; Sampayo-Reyes, A; Marcos, R; Hernández, A
Year
2014
Is Peer Reviewed?
Yes
Journal
Archives of Toxicology
ISSN:
0340-5761
EISSN:
1432-0738
Volume
88
Issue
3
Page Numbers
585-596
Language
English
PMID
24190502
DOI
10.1007/s00204-013-1151-0
Web of Science Id
WOS:000331653200005
URL
http://link.springer.com/10.1007/s00204-013-1151-0
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Abstract
Inorganic arsenic (i-As) is a well-established human carcinogen to which millions of people are exposed worldwide. It is generally accepted that the genotoxic effects of i-As after an acute exposure are partially linked to the i-As-induced production of reactive oxygen species, but it is necessary to better determine whether chronic sub-toxic i-As doses are able to induce biologically significant levels of oxidative DNA damage (ODD). To fill in this gap, we have tested the genotoxic and oxidative effects of environmentally relevant arsenic exposures using mouse embryonic fibroblast MEF mutant Ogg1 cells and their wild-type counterparts. Effects were examined by using the comet assay complemented with the use of FPG enzyme. Our findings indicate that MEF Ogg1-/- cells are more sensitive to arsenite-induced acute toxicity, genotoxicity and ODD. Long-term exposure to sub-toxic doses of arsenite generates a detectable increase in ODD and genotoxic DNA damage only in MEF Ogg1-deficient cells. Altogether, the data presented here point out the relevance of ODD and Ogg1 genetic background on the genotoxic risk of i-As at environmentally plausible doses. The persistent accumulation of DNA 8-OH-dG lesions in Ogg1-/- cells during the complete course of the exposure suggests a relevant role in arsenic-associated carcinogenic risk in turn.
Keywords
Arsenic; 8-OH-dG; Ogg1; Oxidative DNA damage; Genotoxic; Comet assay
Tags
IRIS
•
Arsenic Hazard ID
PubMed
Considered New
PubMed
PubMed
Considered New
WOS
Considered New
WOS
ToxNet
Excluded
WOS Duplicates
WOS
ToxNet
Excluded
Toxnet Duplicates
WOS Duplicates
2. Lit Search Updates through Oct 2015
PubMed
WOS
ToxNet
Considered
7. Other Studies through Oct 2015
MOA
•
Arsenic (Inorganic)
1. Literature
Lit search updates through Oct 2015
3. Hazard ID Screening
Other potentially supporting studies
4. Adverse Outcome Pathways/Networks Screening
Relevant
•
Arsenic MOA
4. Adverse Outcome Pathways
Non-oxidative DNA/ chromosomal damage
Oxidative stress related effects (includes non-specific SH reactions)
5. Health Effect
Cancer
1. MOA Literature Screening
Health Effect Screening
•
Arsenic Susceptibility
Life Stages Citation Mapping
15%-20%
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