Celecoxib mitigates genotoxicity induced by ionizing radiation in human blood lymphocytes

Seyed Jalal Hosseinimehr, Mahdieh Fathi, Arash Ghasemi, Seyedeh Nesa Rezaeian Shiadeh, Tayyeb Allahverdi Pourfallah


Ionizing radiation causes DNA damage and chromosome abbreviations on normal cells. The radioprotective effect of celecoxib (CLX) was investigated against genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Peripheral blood samples were collected from human volunteers and were incubated at different concentrations at 1, 5, 10 and 50 μM of CLX for two hours. At each dose point, the whole blood was exposed in vitro to 150 cGy of X-ray, and then the lymphocytes were cultured with mitogenic stimulation to determine the micronucleus frequency in cytokinesis blocked binucleated lymphocytes. Incubation of the whole blood with CLX exhibited a significant decrease in the incidence of micronuclei in lymphocytes induced by ionizing radiation, as compared with similarly irradiated lymphocytes without CLX treatment. The maximum reduction on the frequency of micronuclei was observed at 50 μM of CLX (65% decrease). This data may have an important possible application for the protection of human lymphocytes from the genetic damage induced by ionizing irradiation in human exposed to radiation.


Celecoxib; Genotoxicity; Ionizing radiation; Lymphocyte

Full Text:



Panganiban RA, Snow AL, Day RM. Mechanisms of radiation toxicity in transformed and non-transformed cells. Int J Mol Sci. 2013;14:15931-15958.

Hosseinimehr SJ. Flavonoids and genomic instability induced by ionizing radiation. Drug Discovery Today. 2010;15:907-918.

Kim YM, Shin YK, Jun HJ, Rha SY, Pyo H. Systematic analyses of genes associated with radiosensitizing effect by celecoxib, a specific cyclooxygenase-2 inhibitor. J Radiat Res. 2011;52:752-765.

Milas L. Cyclooxygenase-2 (COX-2) enzyme inhibitors as potential enhancers of tumor radioresponse. Semin Radiat Oncol. 2001;11:290-299.

Kim YM, Jeong IH, Pyo H. Celecoxib enhances the radiosensitizing effect of 7-hydroxystaurosporine (UCN-01) in human lung cancer cell lines. Int J Radiat Oncol Biol Phys. 2012;83:e399-407.

Kim YM, Pyo H. Different cell cycle modulation by celecoxib at different concentrations. Cancer Biother Radiopharm. 2013;28(2):138-145.

Suzuki K, Gerelchuluun A, Hong Z, Sun L, Zenkoh J, Moritake T, et al. Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress. Neuro Oncol. 2013;15(9):1186-1199.

Xue WP, Bai SM, Luo M, Bi ZF, Liu YM, Wu SK. Phase I clinical trial of nasopharyngeal radiotherapy and concurrent celecoxib for patients with locoregionally advanced nasopharyngeal carcinoma. Oral Oncol. 2011;47:753-757.

Smith MR, Manola J, Kaufman DS, Oh WK, Bubley GJ, Kantoff PW. Celecoxib versus placebo for men with prostate cancer and a rising serum prostate-specific antigen after radical prostatectomy and/or radiation therapy. J Clin Oncol. 2006;24:2723-2728.

Rothkamm K, Barnard S, Moquet J, Ellender M, Rana Z, Burdak-Rothkamm S. DNA damage foci: Meaning and significance. Environ Mol Mutagen. 2015;56:491-504.

Borrego-Soto G, Ortiz-Lopez R, Rojas-Martinez A. Ionizing radiation-induced DNA injury and damage detection in patients with breast cancer. Genet Mol Biol. 2015;38(4):420-432.

Geisel D, Zimmermann E, Rief M, Greupner J, Laule M, Knebel F, et al. DNA double-strand breaks as potential indicators for the biological effects of ionising radiation exposure from cardiac CT and conventional coronary angiography: a randomised, controlled study. Eur Radiol. 2012;22(8):1641-1650.

Rastkhah E, Zakeri F, Ghoranneviss M, Rajabpour MR, Farshidpour MR, Mianji F, et al. The cytokinesis-blocked micronucleus assay: dose-response calibration curve, background frequency in the population and dose estimation. Radiat Environ Biophys. 2016;55:41-51.

Hosseinimehr SJ, Nobakht R, Ghasemi A, Pourfallah TA. Radioprotective effect of mefenamic acid against radiation-induced genotoxicity in human lymphocytes. Radiat Oncol J. 2015;33:256-260.

Beetstra S, Thomas P, Salisbury C, Turner J, Fenech M. Folic acid deficiency increases chromosomal instability, chromosome 21 aneuploidy and sensitivity to radiation-induced micronuclei. Mutat Res. 2005;578(1-2):317-326.

Cinkilic N, Tuzun E, Cetintas SK, Vatan O, Yilmaz D, Cavas T, et al. Radio-protective effect of cinnamic acid, a phenolic phytochemical, on genomic instability induced by X-rays in human blood lymphocytes in vitro. Mutat Res Genet Toxicol Environ Mutagen. 2014;770:72-79.

Rostami A, Moosavi SA, Dianat Moghadam H, Bolookat ER. Micronuclei Assessment of the radioprotective effects of melatonin and vitamin c in human lymphocytes. Cell J. 2016;18:46-51.

Wu J, Lyons GH, Graham RD, Fenech MF. The effect of selenium, as selenomethionine, on genome stability and cytotoxicity in human lymphocytes measured using the cytokinesis-block micronucleus cytome assay. Mutagenesis. 2009;24:225-232.

Fenech M. The in vitro micronucleus technique. Mutat Res. 2000;455:81-95.

Dongari N, Sauter ER, Tande BM, Kubatova A. Determination of Celecoxib in human plasma using liquid chromatography with high resolution time of flight-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;955-956:86-92.

Park MS, Shim WS, Yim SV, Lee KT. Development of simple and rapid LC-MS/MS method for determination of celecoxib in human plasma and its application to bioequivalence study. J Chromatogr B Analyt Technol Biomed Life Sci. 2012;902:137-141.

Zarghi A, Shafaati A, Foroutan SM, Khoddam A. Simple and rapid high-performance liquid chromatographic method for determination of celecoxib in plasma using UV detection: application in pharmacokinetic studies. J Chromatogr B Analyt Technol Biomed Life Sci. 2006;835:100-104.

Chen KH, Hsu CC, Song WS, Huang CS, Tsai CC, Kuo CD, et al. Celecoxib enhances radiosensitivity in medulloblastoma-derived CD133-positive cells. Childs Nerv Syst. 2010;26:1605-1612.

Kang KB, Wang TT, Woon CT, Cheah ES, Moore XL, Zhu C, et al. Enhancement of glioblastoma radioresponse by a selective COX-2 inhibitor celecoxib: inhibition of tumor angiogenesis with extensive tumor necrosis. Int J Radiat Oncol Biol Phys. 2007;67:888-896.

Pruthi RS, Derksen JE, Moore D, Carson CC, Grigson G, Watkins C, et al. Phase II trial of celecoxib in prostate-specific antigen recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. Clin Cancer Res. 2006;12:2172-2177.

Mukherjee D, Coates PJ, Lorimore SA, Wright EG. Responses to ionizing radiation mediated by inflammatory mechanisms. J Pathol. 2014;232(2):289-299.

De Sanctis S, De Amicis A, Di Cristofaro S, Franchini V, Regalbuto E, Mammana G, et al. Cytokinesis-block micronucleus assay by manual and automated scoring: calibration curves and dose prediction. Health Phys. 2014;106:745-749.

Heylmann D, Rodel F, Kindler T, Kaina B. Radiation sensitivity of human and murine peripheral blood lymphocytes, stem and progenitor cells. Biochim Biophys Acta. 2014;1846:121-129.

Senbel AM, AbdelMoneim L, Omar AG. Celecoxib modulates nitric oxide and reactive oxygen species in kidney ischemia/reperfusion injury and rat aorta model of hypoxia/reoxygenation. Vascul Pharmacol. 2014;62:24-31.

Ahmed S, Gul S, Gul H, Zia-Ul-Haq M, Ercisli S. Cyclooxygenase-2 inhibition improves antioxidative defense during experimental hypercholesterolemia. Bosn J Basic Med Sci. 2014;14:63-69.

Matthias C, Schuster MT, Zieger S, Harreus U. COX-2 inhibitors celecoxib and rofecoxib prevent oxidative DNA fragmentation. Anticancer Res. 2006;26:2003-2007.


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Creative Commons LicenseThis work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.