Genotoxic Damage To Glioblastoma Cells Treated With 6 Mv X-Radiation in the Presence Or Absence of Methoxy Estradiol, Iudr Or Topotecan

Objective: to explore the cumulative genotoxic damage to glioblastoma (gbm) cells,grown as multicellular spheroids, following exposure to 6 mv x-rays (2 gy, 22 gy) with orwithout, 2- methoxy estradiol (2me2), iododeoxyuridine (iudr) or topotecan (tpt), usingthe picogreen assay.materials and methods: the u87mg cells cultured as spheroids were treated with 6mv x-ray using linear accelerator. specimens were divided into five groups and irradiatedusing x-ray giving the dose of 2 gy after sequentially incubated with one ofthe following three drug combinations: tpt, 2-me2/tpt, iudr/tpt or 2me2/iudr/tpt. one specimen was used as the irradiated only sample (r). the last group wasalso irradiated with total dose of 22 gy (each time 2 gy) of 6 mv x-ray in 11 fractionsand treated for three times. dna damage was evaluated using the picogreen methodin the experimental study.results: r/tpt treated group had more dna damage [double strand break (dsb)/singlestrand break (ssb)] compared with the untreated group (p < 0.05). moreover the r/tpt group treated with 2me2 followed by iudr had maximum dna damage in spheroidgbm indicating an augmented genotoxicity in the cells. the dna damage was inducedafter seven fractionated irradiation and two sequential treatments with 2me2/iudr/tpt.to ensure accuracy of the slope of dose response curve the fractionated radiation wascalculated as 7.36 gy with respect to ?/b ratio based on biologically effective dose (bed)formulae.conclusion: cells treated with 2me2/iudr showed more sensitivity to radiation andaccumulative dna damage. dna damage was significantly increased when gbmcells treated with tpt ceased at s phase due to the inhibition of topoisomeraseenzyme and phosphorylation of chk1 enzyme. these results suggest that r/tpttreatedcells increase sensitivity to 2me2 and iudr especially when they are usedtogether. therefore, due to an increase in the level of dna damage (ssb vs. dsb)and impairment of dna repair machinery, more cell death will occur. this in turn mayimprove the treatment of gbm.