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Original

Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells

, , , , &
Pages 718-728 | Received 06 Apr 2009, Published online: 19 Jan 2010
 

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

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