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As(III) transcriptionally activates the gadd45a gene via the formation of H2O2.

Authors
Bower-JJ; Leonard-SS; Chen-F; Shi-X
Source
Free Radic Biol Med 2006 Jul; 41(2):285-294
NIOSHTIC No.
20030626
Abstract
Arsenic is a ubiquitous environmental contaminant associated with increased risks of human cancers of the skin, lung, bladder, and prostate. Intriguingly, it is also used to treat certain types of leukemia. It has recently been suggested that these paradoxic effects may be mediated by arsenic's ability to simultaneously activate DNA damage and apoptotic and transformation pathways. Here, we investigate the effects of arsenic exposure on the induction of the growth arrest and DNA damage protein 45a (GADD45a), which is thought to play roles in apoptosis, DNA damage response, and cell cycle arrest. We found that arsenic transcriptionally activates the gadd45a promoter located in a 153-bp region between -234 and -81, relative to the transcriptional start site. In addition, this transcriptional induction was abrogated in the presence of H2O2 scavengers, suggesting a role for H2O2 in the transcriptional control of the gadd45a gene through a Fenton-like free radical mechanism.
Keywords
Genes; Environmental-contamination; Arsenic-compounds; Cancer; Skin-cancer; Risk-factors; Risk-analysis; Lung-cancer; Bladder-cancer; Prostate-cancer; DNA-damage; Arsenites; Arsenic-poisoning
CODEN
FRBMEH
CAS No.
7440-38-2
Publication Date
20060701
Document Type
Journal Article
Email Address
xshi@cdc.gov
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
2
ISSN
0891-5849
NIOSH Division
HELD
Priority Area
Research Tools and Approaches: Cancer Research Methods
Source Name
Free Radical Biology and Medicine
State
WV
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