Mitochondrial oxidative stress elicits chromosomal instability after exposure to isocyanates in human kidney epithelial cells.
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 microM 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.
Mishra
Pradyumna K
PK
Bhopal Memorial Hospital & Research Centre, Bhopal, India. pkm_8bh@yahoo.co.uk
Raghuram
Gorantla V
GV
Panwar
Hariom
H
Jain
Deepika
D
Pandey
Hemant
H
Maudar
Kewal K
KK
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000941:Antigens / Q000032:analysis; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D002503:Centromere / Q000187:drug effects / Q000648:ultrastructure; D043171:Chromosomal Instability / Q000187:drug effects*; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000187:drug effects* / Q000235:genetics; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005980:Glutathione Reductase / Q000032:analysis; D006801:Humans; D017953:Isocyanates / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000032:analysis; D000099156:Superoxide Dismutase 2
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000941:Antigens; D003849:Deoxyguanosine; D005980:Glutathione Reductase; D017953:Isocyanates; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C086178:pericentrin