Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals

Nilanjana Banerjee, Mayukh Banerjee, Sudipto Ganguly, Santu Bandyopadhyay, Jayanta K. Das, Apurba Bandyopadhay, Mitali Chatterjee, Ashok K. Giri

Research output: Contribution to journalArticle

Abstract

In West Bengal, India, more than 6 million people in nine districts are exposed to arsenic through drinking water. It is regarded as the greatest arsenic calamity in the world. Arsenic is a well-documented human carcinogen, which does not induce cancer in any other animal model. Interestingly, at lower concentrations, arsenic is known to induce apoptosis in various cancer cell lines in vitro. We have studied apoptosis in human peripheral blood mononuclear cells (PBMC) of 30 arsenic exposed skin lesion individuals by annexin V-FITC staining and compared with 28 unexposed individuals. The percentage of apoptotic cells in individuals with skin lesions was significantly higher (p < 0.001) in comparison to unexposed individuals. In the exposed individuals with skin lesions, there were elevated levels of intracellular reactive oxygen species (ROS), mitochondrial membrane permeability and increased cytochrome c release, leading to increased downstream caspase activity. Arsenic-induced DNA damage was confirmed by DNA ladder formation and confocal microscopy. We also observed that chronic arsenic exposure reduced Bcl-2/Bax ratio and also resulted in cell cycle arrest of PBMC in G0/G1 phase. All these observations indicate that mitochondria-mediated pathway may be responsible for arsenic-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)101-111
Number of pages11
JournalToxicology
Volume246
Issue number2-3
DOIs
StatePublished - Apr 18 2008
Externally publishedYes

Keywords

  • 6-Carboxy-2,7-dichlorodihydrofluorescein diacetate (DCFDA)
  • Arsenic
  • Caspase
  • Mitochondria
  • Rhodamine123 (RH123)
  • Skin lesions

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Banerjee, N., Banerjee, M., Ganguly, S., Bandyopadhyay, S., Das, J. K., Bandyopadhay, A., Chatterjee, M., & Giri, A. K. (2008). Arsenic-induced mitochondrial instability leading to programmed cell death in the exposed individuals. Toxicology, 246(2-3), 101-111. https://doi.org/10.1016/j.tox.2007.12.029