Necrosis induction by various radiation modalities in human glioblastoma multiforme tumor cells versus normal human astrocytes.

摘要

Glioblastoma multiforme is the most commonly diagnosed brain cancer, but there is currently no effective treatment and most patients do not survive past 18 months of diagnosis. When patients undergo radiation treatment, normal tissue is also hit. Because of this, it is important to understand the damaging effects radiation has on normal tissue. The goal of this study is to determine the mode of radiation-induced cell death in normal human astrocyte (NHA) and glioblastoma multiforme (U87 and U251 GBM) brain cancer cells by analyzing morphological indicators of programmed cell death pathways (autophagy, oncosis, and necrosis) using the morphology of cell death (MCD) database that I generated. TEM images were collected after various time points (3 or 7 days post irradiation) and using various modes of radiation (gamma, fast neutron, modified enhanced thermal neutron beam, and modified enhanced thermal neutron beam with gadolinium neutron capture). Images were then analyzed for mode of cell death. Preliminary analysis of the MCD database has already yielded results that may have significant therapeutic implications. Fast neutrons were found to induce high levels of necrosis. This most likely contributes to radiation gliosis which is the lethal side effect seen after patients undergo fast neutron treatment. It was also found that after modified enhanced thermal neutron beam with gadolinium neutron capture treatment, necrosis was not induced above background levels. Autophagy data indicate that cells die with autophagy and in many cases also oncosis. In the gadolinium neutron capture treatments, the highest clonogenic cell death was observed for GBM cells. These data suggest that gadolinium neutron capture is the most effective of the four radiation modalities tested at killing GBM cell and it does not induce necrosis. The lack of radiation-induced necrosis should benefit patients by reduction or elimination of a lethal side effect, radiation gliosis. Clearly, this database will be a rich source of information in the study of cancer biology and radiation biology for years to come.