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Eyvazzadeh N, Neshasteh-Riz A, Mahdavi SR, et al. Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan. Cell J. 2015;17(2):312-21doi: 10.22074/cellj.2016.3738.
Eyvazzadeh, N., Neshasteh-Riz, A., Mahdavi, S. R., & Mohsenifar, A. (2015). Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan. Cell journal, 17(2), 312-21. https://doi.org/10.22074/cellj.2016.3738
Eyvazzadeh, Nazila, et al. "Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan." Cell journal vol. 17,2 (2015): 312-21. doi: https://doi.org/10.22074/cellj.2016.3738
Eyvazzadeh N, Neshasteh-Riz A, Mahdavi SR, Mohsenifar A. Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan. Cell J. 2015;17(2):312-21. doi: 10.22074/cellj.2016.3738. Epub 2015 Jul 11. PMID: 26199910; PMCID: PMC4503845.
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Cell J. 2015;17(2):312-21. doi: 10.22074/cellj.2016.3738. Epub 2015 Jul 11.

Genotoxic Damage to Glioblastoma Cells Treated with 6 MV X-Radiation in The Presence or Absence of Methoxy Estradiol, IUDR or Topotecan.

Cell journal

Nazila Eyvazzadeh, Ali Neshasteh-Riz, Seyed Rabee Mahdavi, Afshin Mohsenifar

Affiliations

  1. Radiation Research Center, Faculty of Paramedicine, AJA University of Medical Sciences, Tehran, Iran.
  2. Department of Radiology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran.
  3. Department of Medical Physics, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
  4. Research and Department Nanozino, Tehran, Iran.

PMID: 26199910 PMCID: PMC4503845 DOI: 10.22074/cellj.2016.3738

Abstract

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 or without, 2- methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay.

MATERIALS AND METHODS: The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided into five groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the 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 was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study.

RESULTS: R/TPT treated group had more DNA damage [double strand break (DSB)/single strand 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 spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/β ratio based on biologically effective dose (BED) formulae.

CONCLUSION: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPT- treated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. 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 may improve the treatment of GBM.

Keywords: 2-Methoxyestradiol; DNA Damage; HIF-1Alpha; Picogreen; Topotecan

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