Increasing Radiosensitivity with histamine in 1205 Lu human melanoma cells

MELISA NICOUD; DIEGO MARTINEL LAMAS; NOELIA MASSARI; VANINA MEDINA

Málaga

Congreso; European Histamine Research Society, 44th Annual Meeting; 2015

Melanoma is a highly metastatic cancer, which is markedly resistant to conventional therapy and its global incidence continues to increase. It was previously reported the expression of histamine receptors in melanoma cell lines and a role for histamine in melanoma cell growth. In addition, the radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine and gamma radiation in vitro and in vivo on the radiobiological response of 1205Lu human melanoma cells and to explore the potential molecular mechanisms of the radiosensitizing action. For this purpose, we evaluated the response to gamma radiation (0 to 6 Gy). Cells were treated with histamine (10 µM) 24 h before irradiation and radiobiological parameters, including 2 Gy dose (D) surviving fraction (SF2Gy), were obtained from the survival curves adjusted to the linear quadratic model [SF=e-(D+D2)]. Cell apoptosis was determined by the TUNEL assay and Annexin-V staining, while DNA damage was investigated through evaluating the levels of 8-hydroxy-2-deoxyguanosine and gamma-H2AX after 2 Gy dose. Antioxidant enzymes? activity and reactive oxygen species (ROS) levels were measured spectrophotometrically and by flow cytometry, respectively. Result indicate that histamine increased radiosensitivity of 1205Lu cells (SF2Gy 0.14±0.03 vs. 0.34±0.02 in untreated cells; α 1.06±0.01 vs. 0.42±0.07 in untreated cells, P