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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.
| Abbreviations | ||
| 8-oxo-dG | = | 8-hydroxy-2′deoxy guanosine |
| CIN | = | Chromosomal instability |
| CDK | = | Cyclin-dependent kinase |
| CMH2DCFDA | = | 2′-7′- dichlorodihydrofluorescein diacetate |
| EMEM | = | Eagle's Minimal Essential Medium |
| FISH | = | Fluorescence in-situ hybridization |
| GR | = | Glutathione reductase |
| GCRs | = | Gross chromosomal rearrangements |
| GSH | = | Glutathione |
| HEK-293 | = | human kidney epithelial cell |
| MIC | = | Methyl isocyanate |
| ROS | = | Reactive oxygen species |
| SKY | = | Spectral karyotyping |
| SOD | = | Superoxide dismutase |
| Abbreviations | ||
| 8-oxo-dG | = | 8-hydroxy-2′deoxy guanosine |
| CIN | = | Chromosomal instability |
| CDK | = | Cyclin-dependent kinase |
| CMH2DCFDA | = | 2′-7′- dichlorodihydrofluorescein diacetate |
| EMEM | = | Eagle's Minimal Essential Medium |
| FISH | = | Fluorescence in-situ hybridization |
| GR | = | Glutathione reductase |
| GCRs | = | Gross chromosomal rearrangements |
| GSH | = | Glutathione |
| HEK-293 | = | human kidney epithelial cell |
| MIC | = | Methyl isocyanate |
| ROS | = | Reactive oxygen species |
| SKY | = | Spectral karyotyping |
| SOD | = | Superoxide dismutase |