CONICET | Buscador de Institutos y Recursos Humanos

We have previously reported that histamine (HA) enhances radiosentivity of malignant cells and also protects normal tissues from high doses of ionizing radiation. In order to investigate the molecular mechanism underlying these effects, we evaluated the capacity of HA to modulate the activity of antioxidant enzymes. We studied the action of HA on the cell lines MDA-MB-231 (human breast carcinoma), WM35 (melanoma) and PANC-1 (pancreatic carcinoma). The levels of intracellular reactive oxygen species (ROS) were assessed by flow-cytometric analysis employing specific fluorescent dyes. The activity of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) was evaluated in cell extracts by spectrophotometric techniques. HA treatment produced a significant decrease in cell proliferation and this effect was correlated with a marked increase in H2O2 while O2·- levels showed minor changes. The activity of SOD and CAT was significantly modified by HA. HA produced two-fold increase and more than five-fold increase in SOD activity in WM35 and PANC-1 cells, respectively. In contrast, HA produced a two-fold decrease in MDA-MB-231 cells? SOD activity. On the other hand, HA exerted a two-fold and three-fold decrease in CAT activity in WM35 and MDA-MB-231 cells respectively while increased CAT activity in PANC-1 cells. Interestingly, the effect produced by HA on SOD activity was inversely correlated with basal activity of this enzyme that was 105 ±10; 370 ± 25; 22 ± 5; units of SOD per mg of protein (U/mg) in WM35, MDA-MB-231 and PANC-1 cells, respectively. The present data indicate that the selective effect exerted by HA on cell proliferation and on cellular response to ionizing radiation is related in part to the modulation of ROS and activity of antioxidant enzymes. poster

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