Modulatory effect of hydrogen peroxide on tumoral lymphocytes proliferation.

ROBERTO DAVICINO; MARIA GABRIELA MANUELE; GRACIELA FERRARO; BLAS MICALIZZI; CLAUDIA ANESINI

IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY

Taylor and Francis

Lugar: USA; Año: 2008

0892-3973

BW 5147 is a murine lymphoma cell line with a high proliferation rate. The aim of this study was to analyze the effect of H2O2 in cell proliferation, studing mainly its effects on the ERK and P-38 pathways. The participation of  nitric oxide and apoptosis in such mechanism was analyzed. Enzymes involved in the regulation of H2O2 levels as superoxide dismutase (SOD) and peroxidase (PER) were analyzed. H2O2 exerted a biphasic effect, that is, cell proliferation  was inhibited at 10-5 M - 10-3 M H2O2, whereas 10-7-10-13 M H2O2 stimulated it. The inhibitory effect of H2O2 was related to the activation of the ERK pathway, NO pruduction and apoptosis because such effects were reverted by UO126.  The  P38 pathway was also involved (effects reverted by SB 203580). On the other hand, the proliferative effect was also related to the activation of ERK and P-38 pathways. The high proliferation rate of these cells was associated with a low level of H2O2 related to a low SOD activity and a high PER activity. In these cell types, the discovery of drugs capable of producing an increase in H2O2 levels could be clinically useful for the treatment of cancer.     Key words : Hydrogen peroxide, lymphoma cell line,  ERK pathway, P-38 pathway, nitric oxide.