Mitochondrial oxidative stress causes chromosomal instability of mouse embryonic fibroblasts.
Aging Cell
; 2(5): 277-85, 2003 10.
Article
en En
| MEDLINE
| ID: mdl-14570235
ABSTRACT
Reactive oxygen species are an inevitable by-product of mitochondrial respiration. It has been estimated that between 0.4 and 4% of molecular oxygen is converted to the radical superoxide (O2*-) and this level is significantly influenced by the functional status of the mitochondria. It is well established that exogenous oxidative stress and high doses of mitochondrial poisons such as paraquat and carbonyl cyanide 4 (trifluoromethoxy) phenylhydrazone (FCCP) can lead to genomic instability. In this report we show for the first time that endogenous mitochondrial oxidative stress in standard cell culture conditions results in nuclear genomic instability in primary mouse embryonic fibroblasts (MEFs). We show that lack of mitochondrial superoxide dismutase in MEFs leads to a severe increase of double strand breaks, end-to-end fusions, chromosomal translocations, and loss of cell viability and proliferative capacity. Our results predict that endogenous mitochondrial oxidative stress can induce genomic instability, and therefore may have a profound effect in cancer and aging.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
/
Inestabilidad Cromosómica
/
Fibroblastos
/
Mitocondrias
Tipo de estudio:
Etiology_studies
Límite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Aging Cell
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos