Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

Arsenic mediates cell proliferation and gene expression in the bladder epithelium: association with activating protein-1 transactivation.

Authors
Simeonova-PP; Wang-S; Toriuma-W; Kommineni-V; Matheson-J; Unimye-N; Kayama-F; Harki-D; Ding-M; Vallyathan-V; Luster-MI
Source
Cancer Res 2000 Jul; 60(13):3445-3453
NIOSHTIC No.
20020812
Abstract
Although the mechanism of action has not yet been defined, epidemiological studies have demonstrated an association between elevated arsenic levels in drinking water and the incidence of urinary bladder transitional cell carcinomas. In the current studies, we demonstrate that mice exposed to 0.01% sodium arsenite in drinking water develop hyperplasia of the bladder urothelium within 4 weeks of exposure. This was accompanied by the accumulation of inorganic trivalent arsenic, and to a lesser extent dimethylarsinic acid, in bladder tissue, as well as a persistent increase in DNA binding of the activating protein (AP)-1 transcription factor. AP-1 transactivation by arsenic also occurred in bladders of transgenic mice containing an AP-1 luciferase reporter. Consistent with these in vivo observations, arsenite increased cell proliferation and AP-1 DNA binding in a human bladder epithelial cell line. Gene expression studies using RNase protection assays, reverse transcription-PCR, and cDNA microarrays indicated that arsenite alters the expression of a number of genes associated with cell growth, such as c-fos, c-jun, and EGR-1, as well as cell arrest, such as GADD153 and GADD45. The proliferation-enhancing effect of arsenic on uroepithelial cells likely contributes to its ability to cause cancer.
Keywords
Arsenic-compounds; Genes; Bladder-disorders; Epidemiology; Carcinomas; Bladder-tissue; Exposure-assessment; Exposure-levels; Laboratory-animals; Animals; Animal-studies; Cancer
Contact
Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, NIH, 1095 Willowdale Road, Morgantown, WV 26505
CODEN
CNREA8
CAS No.
7440-38-2
Publication Date
20000701
Document Type
Journal Article
Email Address
phs9@cdc.gov
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
13
ISSN
0008-5472
NIOSH Division
HELD
Source Name
Cancer Research
State
WV
TOP