Science Inventory

DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS.

Citation:

Sen, B., A. Wang, S D. Hester, J. L. Robertson, AND D C. Wolf. DIMETHYLARSINIC ACID ALTERS EXPRESSION OF OXIDATIVE STRESS AND DNA REPAIR GENES IN A DOSE DEPENDENT MANNER IN THE TRANSITIONAL EPITHELIUM OF THE URINARY BLADDER FROM FEMALE F344 RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.

Description:

Dose-dependent alteration of oxidative stress and DNA repair gene expression by Dimethylarsinic acid [DMA(V)] in transitional epithelium of urinary bladder from female F344 rats.
Arsenic (As) is a major concern as millions of people are at risk from drinking arsenic contaminated water. As exposure is associated with an increased incidence of urinary bladder cancer. DMA(V) is a major methylated metabolite of inorganic As and results in
dose-dependent increase in urinary bladder tumors in F344 rats. The tumors arise from the transitional epithelium. Study of this target cell population is critical in understanding molecular events that develop following exposure. Enhanced cell proliferation, oxidative damage, and loss of DNA repair fidelity are implicated in As mediated toxicity and carcinogenicity. Simultaneous interactions of these effects may be important in As mediated neoplasia in the transitional epithelium of the urinary bladder. Female F344 rats were treated with DMA(V) (1, 4, 40 or 100 ppm) in the drinking water continuously for 28 days. After treatment, rats were euthanized, the bladder removed, flushed with saline, infused with Trizol TM and the contents were removed and frozen. Total RNA from the transitional epithelium was extracted and gene expression analysis using a custom spotted array with 4,362 rat genes was performed. Analysis (GeneSpringTM) showed that 6.5% of all genes passed the statistical Filter (1 way ANOVA, p<0.05). Genes involved in DNA repair and cellular response to oxidative stress were significantly altered. DMA(V) was also modulated expression of genes associated with protein degradation and several oncogenes. There was a dose-dependent response to the pattern of gene expression. As compared with controls, expression levels of most genes were up to 3-fold increased after 4ppm and decreased after 40ppm. Detection of genome wide dose-dependent effects in the target cell population may result in the development of reliable and sensitive markers of As toxicity and carcinogenicity. This abstract does not reflect EPA policy.

Record Details:

Record Type: DOCUMENT (PRESENTATION/ABSTRACT)
Product Published Date: 03/23/2004
Record Last Revised: 02/26/2007
Record ID: 66359

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

ENVIRONMENTAL CARCINOGENESIS DIVISION

CANCER BIOLOGY BRANCH