Carcinogenesis, Vol 18, 569-574, Copyright © 1997 by Oxford University Press
S Arbault, P Pantano, N Sojic, C Amatore, M Best-Belpomme, A Sarasin and M Vuillaume
We present here a real-time and single cell study of an oxidative stress
mechanism in human fibroblasts. Hydrogen peroxide released by a single
normal or SV40-transformed human fibroblast was detected at the surface of
an ultramicroelectrode while puncturing the cell membrane with the
ultramicroelectrode tip itself or with a micropipette. This mechanical
intrusion induced the emission of large quantities (10(-15)- 10(-14) mol)
of H2O2 by the cell with a very short time delay (<0.5 s). We show that
this H2O2 production was an active neo-production by fibroblasts when the
membrane was stressed by the cellular puncture and is a model which could
mimic similar effects as particle (virus, bacteria, etc.) intrusion into
the cell. Cell incubations in the presence of some inhibitors of the
different NADPH oxidase enzymes, using ultramicroelectrode measurements of
the short time effects (<20 min) let us believe that an NADPH
oxidase-like enzyme may be implicated in this induced-H2O2 generation.
Phenylarsine oxide (PAO), a specific NADPH oxidase inhibitor, at
concentrations between 0.5-50 microM seemed to quickly kill the transformed
cells preferentially to the normal cells, pointing out for the future a
possible anti-cancerous chemotherapic use.
ARTICLES
Activation of the NADPH oxidase in human fibroblasts by mechanical intrusion of a single cell with an ultramicroelectrode
UPR 42 CNRS, Ecole Normale Superieure, Paris, France.
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