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Paper Information

Journal:   CELL JOURNAL (YAKHTEH)   SPRING 2008 , Volume 10 , Number 1 (37); Page(s) 57 To 64.
 
Paper: 

CYTOGENETIC DAMAGES FROM IODODEOXYURIDINE -INDUCED RADIOSENSITIVITY WITH AND WITHOUT METHOXYAMINE IN HUMAN GLIOBLASTOMA SPHEROIDS

 
 
Author(s):  NESHASTEHRIZ A.*, SAKI MOHAMMAD, KHOUEI SAMIDEH
 
* MEDICAL PHYSICS DEPARTMENT, IRAN UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
 
Abstract: 
Objective: Iododeoxyuridine-induced Radiosensitivityi (IUdR) is a halogenated thymidine analogue recognized to be effective in vitro and in vivo radiosensitizer in human cancers. It is reported that Methoxyamine (MX) potentiates DNA damages in cancer cells with blocking the repair pathway of IUdR damages. But studies, entirely, are restricted on monolayer culture cells from human colon cancer cells. Spheroids are 3D form of cells that aggregate and grow together which resemble in vivo tumor models in several aspects and the results of such studies can be extended to tumor in vivo. The aim of the current study was to evaluate DNA damages from IUdR and gamma rays with and without Methoxyamine in human Glioblastoma spheroids.
Materials and Methods: The DNA induced damages in U87MG cell line were compared using alkaline comet assay method. Experiments were performed with two different sizes of spheroids (100mm and 300mm).
Results: Evaluation of the effects of IUdR with and without MX pretreatment on spheroids following ionizing radiation showed that MX increased the cell damages of IUdR with and without irradiation in both diameters spheroids. The damages were further increased in 100mm compared with 300mm diameter.
Conclusion: Comparisons of tail moments in spheroids with 100 and 300mm diameter showed that cell damages in larger spheroids, 300
mm, are lesser than smaller one, 100mm. This could be due to existence of G0 cells and cells with longer cycle which IUdR was less incorporated into them. Thus, decrease in IUdR radiosensitization and base wxcision repair (BER), results in reduction of MX activities. Using agents for inhibiting the activities of proteins which are responsible for carrying the cells to G0 may be beneficial in solving such problems.
 
Keyword(s): RADIOSENSITIZATION, SPHEROID, IUDR, METHOXYAMINE, BER
 
References: 
 
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