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Arsenic and urinary bladder cell proliferation.

Authors
Luster-MI; Simeonova-PP
Source
Toxicol Appl Pharmacol 2004 Aug; 198(3):419-423
NIOSHTIC No.
20025473
Abstract
Epidemiologic studies have demonstrated that a close association exists between the elevated levels of arsenic in drinking water and the incidence of certain cancers, including transitional cell carcinomas of the urinary bladder. We have employed in vitro and in vivo models to examine the effects of sodium arsenite on the urinary bladder epithelium. Mice exposed to 0.01% sodium arsenite in drinking water demonstrated hyperproliferation of the bladder uroepithelium within 4 weeks after initiating treatment. This occurred in the absence of amorphous precipitates and was accompanied by the accumulation of trivalent arsenite (iAs5+), and to a lesser extent dimethylarsenic (DMA), arsenate (iAs5+), and monomethylarsenic (MMA) in bladder tissue. In contrast to the bladder, urinary secretion was primarily in the form of DMA and MMA. Arsenic-induced cell proliferation in the bladder epithelium was correlated with activation of the MAP kinase pathway, leading to extracellular signal-regulated kinase (ERK) kinase activity, AP-1 activation, and expression of AP-1-associated genes involved in cell proliferation. Activation of the MAP kinase pathway involved both epidermal growth factor (EGF) receptor-dependent and -independent events, the latter involving Src activation. Studies summarized in this review suggest that arsenic accumulates in urinary bladder epithelium causing activation of specific signaling pathways that lead to chronic increased cell proliferation. This may play a non-epigenetic role in carcinogenesis by increasing the proliferation of initiated cells or increasing the mutational rate.
Keywords
Arsenic-compounds; Epidemiology; Water-sampling; Water-analysis; Cancer; Carcinomas; Bladder-cancer; Bladder-disease; Bladder-disorders; In-vivo-studies; In-vitro-studies; Models; Sodium-compounds; Arsenites; Bladder-tissue; Carcinogenesis
Contact
Inflammatory Disease Teams, Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
CODEN
TXAPA9
CAS No.
7440-38-2; 7440-23-5
Publication Date
20040801
Document Type
Journal Article
Email Address
mluster@cdc.gov
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Issue of Publication
3
ISSN
0041-008X
NIOSH Division
HELD
Source Name
Toxicology and Applied Pharmacology
State
WV
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