Histamine Potentiates Ionizing Radiation-induced DNA damage In Vitro and In Vivo in Human Triple Negative Breast Cancer

D MARTINEL LAMAS; MELISA N NICOUD; JUAN C PERAZZO; ELENA RIVERA; MEDINA VANINA

Congreso; European Histamine Research Society, 45th Annual Meeting; 2016

We previously demonstrated that histamine selectively increases the radiosensitivity of different human cancer cell lines (MDA-MB-231, MCF-7, 1205Lu). The aims of this work were to investigate the combined effect of histamine and gamma radiation in vitro on markers of DNA damage and antioxidant enzymes´ activity of two triple negative breast cancer (TNBC) cell lines (MDA-MB-231 and MDA-BrM2) and to evaluate the histamine-induced radiosensitization in vivo in MDA-MB-231 TNBC model. Results demonstrate that histamine enhanced radiosensitivity of MDA-BrM2 cells, which display increased brain metastatic activity, mainly through the H1R as previously described for MDA-MB-231 cells. In addition, histamine increased radiation (2 Gy dose)-induced genotoxic activity in both cell lines evidenced by an enhanced number of H2AX foci (marker of DNA double-strand breaks) per cell (4.5±0.9 in control, 23.3±1.7 in 2 Gy-untreated and 33.1±1.9 in 2 Gy-histamine, P