196
Views
10
CrossRef citations to date
0
Altmetric
Original Articles

Gene Expression Changes and Induction of Cell Proliferation by Chronic Exposure to Arsenic of Mouse Testicular Leydig Cells

&
Pages 1150-1154 | Accepted 28 Aug 2006, Published online: 07 Jun 2007
 

Abstract

Arsenic is an important environmental carcinogen that affects millions of people worldwide through contaminated water supplies. Chronic exposure of arsenic has been shown to induce malignant transformation of mammalian cells; however, the mechanism underlying arsenic-induced carcinogenesis is not clear. The (1) induction in the cell proliferation, (2) decrease in DNA repair capacity resulting in the accumulation of mutations, and (3) changes in the DNA methylation patterns affecting regulation of genes are hallmarks of cancer development. Thus, the purpose of this study was to determine whether long-term exposure of both low and high concentrations of arsenic can perturb cell proliferation, DNA repair, and the maintenance of DNA methylation status in TM3 cells, an immortalized Leydig cell derived from normal mouse testis. The effect of arsenic on cell proliferation was determined by cell count data, and arsenic-induced gene expression changes were measured by quantitative real-time polymerase chain reduction (PCR). The results this study revealed a concentration-dependent induction of cell proliferation by arsenic. Increased expression of cell proliferation marker genes (PCNA, CyclinD1) and DNA methylation (DNA Methyl Transferase I) and decreased expression of genes for DNA repair (DNA Polymerase β, ERCC6) with lower concentrations of arsenic was also observed. Thus, the findings of this study are novel, as they indicate a mechanism for arsenic-induced cancers. This is based on the observed increase in cell proliferation and decrease in the capacity of cells to maintain its genomic stability. Our study provides the evidence that arsenic may play a role in the etiology of testicular cancer.

This work was supported by a grant (RR03045) from National Institutes of Health.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.