Cell Journal (Jan 2008)
Cytogenetic Damages from Iododeoxyuridine -induced Radiosensitivity with and without Methoxyamine in Human Glioblastoma Spheroids
Abstract
Objective: Iododeoxyuridine-induced Radiosensitivityi (IUdR) is ahalogenated thymidine analogue recognized to be effective in vitro andin vivo radiosensitizer in human cancers. It is reported that Methoxyamine (MX)potentiates DNA damages in cancer cells with blocking the repair pathway ofIUdR damages. But studies, entirely, are restricted on monolayer culture cellsfrom human colon cancer cells. Spheroids are 3D form of cells that aggregateand grow together which resemble in vivo tumor models in several aspects andthe the results of such studies can be extended to tumor in vivo. The aim of thecurrent study was to evaluate DNA damages from IUdR and gamma rays withand without Methoxyamine in human Glioblastoma spheroids.Materials and Methods: The DNA induced damages in U87MG cell line werecompared using alkaline comet assay method. Experiments were performedwith two different sizes of spheroids (100μm and 300μm).Results: Evaluation of the effects of IUdR with and without MX pretreatmenton spheroids following ionizing radiation showed that MX increased the celldamages of IUdR with and without irradiation in both diameters spheroids. Thedamages were further increased in 100μm compared with 300μm diameter.Conclusion: Comparisons of tail moments in spheroids with 100 and 300μmdiameter showed that cell damages in larger spheroids, 300μm, are lesserthan smaller one, 100μm. This could be due to existence of G0 cells and cellswith longer cycle which IUdR was less incorporated into them. Thus, decreasein IUdR radiosensitization and base wxcision repair (BER), results in reductionof MX activities. Using agents for Inhibiting the activities of proteins whichare responsible for carrying the cells to G0 may be beneficial in solving suchproblems.
