A. Korzets et al., H2O2 induces DNA repair in mononuclear cells: Evidence for association with cytosolic Ca2+ fluxes, J LA CL MED, 133(4), 1999, pp. 362-369
Citations number
28
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Cellular DNA repair systems are induced whenever DNA is damaged. Reactive o
xygen species (ROS) are generated, in vivo, in the tissues as a result of r
egular cellular metabolism or after exposure to oxidizing agents, such as u
ltraviolet (UV) irradiation. It has been suggested that ROS mediate DNA dam
age. The objectives of the study were as follows: (1) to investigate whethe
r hydrogen peroxide (H2O2), the commonly occurring cellular ROS, induces DN
A repair as a response to the damage it probably causes; (2) to evaluate wh
ether H2O2-induced DNA repair, if present, is signaled through a Ca2+-depen
dent pathway via the tyrosine kinase signal transduction. H2O2 was found to
induce DNA repair in human peripheral blood mononuclear cells (PBMCs) in a
dose-dependent manner. The recovery of RNA synthesis, which occurred after
DNA repair, confirmed that transcribable DNA was repaired. The inhibition
of tyrosine kinase activity by genistein reduced the DNA repair significant
ly. Furthermore, H2O2 caused a dose-dependent significant rise in cytosolic
calcium ((Ca2+)i). H2O2 also induced a small rise in (Ca2+)i of cytosolic
Ca2+-depleted cells, probably reflecting the release of Ca2+ from internal
stores. Genistein inhibited both Ca2+ influx and Ca2+ release from internal
stores. In summary, H2O2 induced a DNA repair synthesis that was in part C
a2+ dependent and signaled via tyrosine kinase. The changes in DNA repair p
aralleled changes in (Ca2+)i. The H2O2-induced (Ca2+)i rise was mostly the
result of influx, but to some degree it was also due to the translocation o
f Ca2+ from internal stores.