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 |