Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells

  • Authors:
    • Kamaleshwar P. Singh
    • James W. DuMond
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.253
  • Pages: 253-260
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Abstract

Arsenic is an important environmental carcinogen that affects millions of people worldwide through contaminated water supplies. Genotoxicity of arsenic has been a topic of controversy. Both genetic alterations (mutations) and epigenetic changes (methylation) have been shown to play a crucial role in environmental carcinogenesis. Chronic exposure to arsenic has been shown to induce malignant transformation of mammalian cells. However, the genetic aberrations induced by arsenic in this process are unclear. The purpose of this study was to determine if both lower (1 pg/ml) and higher concentrations (100 ng/ml) of arsenic induces either mutations or methylation changes that could lead to the development of genomic instability in TM3 cells, immortalized Leydig cells derived from normal mouse testis. Two independent exposure times were used in this study which resulted in cells of 33 and 100 generations in age. Arsenic-induced genetic and epigenetic changes were screened at a genome-wide level by random amplified polymorphic DNA (RAPD), also known as AP-PCR method with undigested DNA as well as DNA digested by the methylation sensitive isosizomeric restriction enzymes MSPI and HpaII and untreated controls. Changes in the DNA fingerprint of both, the restriction enzyme digested DNA (indicating methylation changes) as well as undigested DNA (indicating mutations) from arsenic-treated (low as well as high dose) samples were observed as compared to their controls. Thus, this study provides the first evidence at DNA sequence level for mutagenic potential of arsenic. Further characterization of these altered genomic regions is underway. The understanding of these genetic and epigenetic changes in arsenic-induced carcinogenesis will provide a basis for better interventional approaches in both the treatment and prevention of arsenic-induced cancer.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Singh KP and DuMond JW: Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells. Int J Oncol 30: 253-260, 2007.
APA
Singh, K.P., & DuMond, J.W. (2007). Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells. International Journal of Oncology, 30, 253-260. https://doi.org/10.3892/ijo.30.1.253
MLA
Singh, K. P., DuMond, J. W."Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells". International Journal of Oncology 30.1 (2007): 253-260.
Chicago
Singh, K. P., DuMond, J. W."Genetic and epigenetic changes induced by chronic low dose exposure to arsenic of mouse testicular Leydig cells". International Journal of Oncology 30, no. 1 (2007): 253-260. https://doi.org/10.3892/ijo.30.1.253