Radioresistencia en glioblastoma: papel de la hipoxia en la genotoxicidad tumoral inducida por radiaciones ionizantes

Abstract

Objective: Glioblastoma multiforme is the most frequent grade IV astrocytoma in adulthood, and is characterized by a high radioresistance, which is associated with the presence of hypoxic regions within the tumor. Considering the important role of hypoxia on the cellular response to ionizing radiation, in this study, we evaluated the relationship between hypoxia, DNA damage and cell survival. Methodology: Two different cellular lines were used, glioblastoma (U87) and breast cancer (MCF-7). The effect of the ionizing radiation on the survival of both cellular lines under conditions of hypoxia and normoxia, was evaluated using the colony forming assay. The DNA damage was evaluated by electrophoresis technique in gel of a single cell or comet testing. Results: The U87 line presented the highest radioresistance under hypoxic conditions at 8 Gy, but less resistance to intermediate doses (6 Gy). MCF-7 shows greater radioresistance under normoxia, although not statistically significant. In the kite assay, MCF-7 presents the major DNA damage by increasing the dose of irradiation in hypoxia, while U87 shows an increase in damage in hypoxia, which is not dose dependent. Conclusion: It was evidenced that in the U87 line, there is not a relation between the increase in DNA damage under hypoxia and vHh DNA repair capacity for this line. In contrast, in the MCF-7 cell line, it is evident that its repair mechanisms are more efficient under nor-moxia conditions.