Role of histamine in irradiated PANC-1 cells proliferation.

NORA MOHAMAD, GRACIELA CRICCO, FERNANDA GENRE, ALICIA GUTIÉRREZ, MARIEL NÚÑEZ, CLAUDIA COCCA, ELENA RIVERA, ROSA BERGOC AND GABRIELA MARTÍN.

Buenos Aires, Argentina

Congreso; XII International Congress of International Radiation Protection Association (IRPA); 2008

International Radiation Protection Association

Radiotherapy may be used to treat non-spread pancreatic cancer which cannot be removed by surgery and also to relieve pain. We have previously reported that histamine, a biogenic amine well established as a growth factor for many neoplasms, modulates the human pancreatic adenocarcinoma cell line PANC-1 proliferation. We have also demonstrated that histamine modifies radiosensitivity of human malignant mammary cells. The aim of this work was to evaluate the action of histamine as a potential radiosensitizer in PANC-1 cells. In order to determine the radiosensitivity parameters, control and histamine treated cells were irradiated with doses ranging from 0 to 5 Gy. Cell cultures were treated with histamine for 24 hs previous and up to 24 hs post-irradiation. Using an adequate software survival curves were plotted and fitted to the linearcuadratic model. Coefficients alpha and beta, alpha/beta ratio and 2 Gy-survival fraction were determined. Radiosensitivity parameters remained unchanged when histamine treated irradiated cells were compared to control irradiated cells. We have determined that hydrogen peroxide and nitric oxide are involved in PANC-1 cells proliferation in a concentration dependent way, being both reactive species histamine regulated. Furthermore, the role of oxygen and nitrogen reactive species in mediating the effects of irradiation is well known. Levels of superoxide anion, hydrogen peroxide and nitric oxide were assessed by flow cytometric analysis using specific fluorescent dyes. The expression of antioxidant enzymes, catalase, superoxide dismutase and glutathione peroxidase was determined by immunoblotting. The modulation of reactive oxygen and nitrogen species produced by ionizing radiation was not modified by histamine treatment. These results would indicate that histamine does not affect radiosensitivity of PANC-1 cells since though it regulates proliferation and reactive species metabolism, ionizing radiation may activate cell mechanisms that can not be counteracted by histamine.