Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells |
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Authors: | Pradyumna K. Mishra Gorantla V. Raghuram Hariom Panwar Deepika Jain Hemant Pandey Kewal K. Maudar |
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Affiliation: | 1. Bhopal Memorial Hospital &2. Research Centre, Bhopal, Indiapkm_8bh@yahoo.co.uk;4. Research Centre, Bhopal, India |
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Abstract: | The role of oxidative stress is often attributed in environmental renal diseases. Isocyanates, a ubiquitous chemical group with diverse industrial applications, are known to undergo bio-transformation reactions upon accidental and occupational exposure. This study delineates the role of isocyanate-mediated mitochondrial oxidative stress in eliciting chromosomal instability in cultured human kidney epithelial cells. Cells treated with 0.005 µM concentration of methyl isocyanate displayed morphological transformation and stress-induced senescence. Along the time course, an increase in DCF fluorescence indicative of oxidative stress, depletion of superoxide dismutase (SOD) and glutathione reductase (GR) and consistent accumulation of 8-oxo-dG were noticed. Thus, endogenous oxidative stress resulted in aberrant expression of p53, p21, cyclin E and CDK2 proteins, suggestive of deregulated cell cycle, chromosomal aberrations, centromeric amplification, aneuploidy and genomic instability. |
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Keywords: | Free radicals mitochondria oxidative stress genomic instability carcinogenesis isocyanates |
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