Radioprotective Effects of Histamine H2 Receptor Antagonists Famotidine and Ranitidine on Gamma-Ray Induced Chromosome Aberration and Micronuclei in vitro in Human Lymphocytes
American Journal of BioScience
Volume 3, Issue 6, November 2015, Pages: 249-255
Received: Dec. 25, 2014;
Accepted: Jan. 5, 2015;
Published: Nov. 13, 2015
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Narinder Kumar Sharma, Radiation Biology and Health Sciences Division, Bio-Sciences Group, Bhabha Atomic Research Centre, Mumbai, India
Histamine H2 receptor antagonist are used in the clinical treatment of peptic ulcer. In vitro metaphase analysis and micronucleus assay were used to test the effect of Famotidine & Ranitidine on 60Cobalt gamma-ray induced clastogenic effects. Heparinised whole blood was obtained from 6 healthy volunteers and was gamma irradiated with 3Gy. Lymphocyte cultures were initiated and aqueous solution of Famotidine (150µg/ml) & Ranitidine (500µg/ml) was added at 0h and 24h. Cultures were harvested & processed at 48h & 72h for chromosome aberrations and micronucleus analysis respectively. At 0h & 24h after 3Gy gamma irradiation, cultures treated with Famotidine & Ranitidine independently showed significant decrease (p < 0.0001) in the frequency of chromosome aberration. At 0h & 24h Famotidine induced 60.91% & 56.42% inhibition in dicentrics & 59.39% & 56.21% inhibition was observed in total aberrations where as Ranitidine induce 52.11% & 43.54% inhibition in dicentrics and 53.06% & 46.66% inhibition in total aberrations at 0h & 24h. Significant decrease in the frequency of micronuclei was observed with Famotidine treatment after 3Gy of gamma irradiation, which induced inhibition of 48.83% (p < 0.0001) at 0hr & 5.02% (p < 0.016) at 24h. However, Ranitidine induced significant decrease (p < 0.0001) in frequency of micronuclei of 28.85% at 0h where as a decrease in frequency was observed of 2.88% at 24h although not significant when compared with 3Gy gamma irradiation alone. In conclusion radio protective effects of Histamine H2 receptor antagonists Famotidine and Ranitidine was observed on exposure togamma-ray.
Narinder Kumar Sharma,
Radioprotective Effects of Histamine H2 Receptor Antagonists Famotidine and Ranitidine on Gamma-Ray Induced Chromosome Aberration and Micronuclei in vitro in Human Lymphocytes, American Journal of BioScience.
Vol. 3, No. 6,
2015, pp. 249-255.
Nikjoo H. Radiation Track and DNA damage. Iran. J. Radiat. Res. 2003, vol. 1: pp. 3-16.
Patt H.M., Tyree E. B. et al. Cysteine protection against X irradiation. Science. 1949, vol. 110: pp. 213-214
Patt H.M., Mayer S. H. et al. Radiation dose reduction by cysteine. J. Cell Comp. Physiol. 1953, vol. 42: pp. 327-341.
Lipsy R.J., Fennerty B.F. et al. Clinical review of histamine H2 receptor antagonists. Arch. Int. Med. 1990, vol. 150: pp. 745-751.
Ghorbani M. and Mozdarani H. In vitro radioprotective effects of histamine H2 receptor antagonists against gamma-rays induced chromosomal aberrations in human lymphocytes Iran. J. Radiat. Res. 2003, vol. 1(2): pp. 99-104.
Mozdarani H. Radioprotective properties of histamine H2 receptor antagnonist: present and Future prospects. J. Radiat. Res. 2003, vol. 44: pp. 145-149.
Krishnaja A.P. and Sharma N.K. Heterogeneity of chromosome damage in β-thalassaemia traits. An evaluation of spontaneous and gamma-ray-induced micronuclei and chromosome aberrations in lymphocytes in vitro after G0 and G2 phase irradiation. Int. J. Radiat. Biol. 1994, vol. 66: pp. 29-39.
Krishnaja A.P., Sharma N.K. On the optimization and application of sister chromatid exchanges (SCEs) and cytokinesis blocked micronuclei (CBMN) in human lymphocytes for cytogenetic monitoring. In: Chauhan P.S., Gopinath P.M. editors. Environmental Mutagenesis and Carcinogenesis, Mumbai: Quest publications. 1998, pp.77-90.
Fenech M. The in vitro micronucleus technique. Mutat. Res. 2000, vol. 455: pp. 81-95.
Fenech M. The cytokinesis blocked micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human population. Mutat. Res. 1993, vol 285: pp. 35-44.
ISCN. International system of cytogenetic nomenclature for acquired chromosome aberrations. Harnden D.G. and Klinger H.P. (eds.), Published in collaboration with Cytogenetic and Cell Genetics, Karger, 1985, pp. 66-73.
International Atomic Energy, Agency. Biological Dosimetry: Chromosomes aberrations analysis for dose assessment, I.A.E.A. Vienna Technical documents. 2001, vol. 405.
Fenech M. Cytokinesis-block micronucleus cytome assay. Nature Protocols. 2007, vol. 2: pp. 1084-1104.
Cole R.J. and Taylor N. Short term tests for transplacentally active carcinogens. I. Micronucleus formation in fetal and maternal mouse erythroblasts. Mutat. Res. 1981, vol. 80: pp.141-57.
Uma Devi P. and Sharma A.S. Mouse bone marrow response to low doses of whole-body gamma irradiation: induction of micronuclei. Int. J. Radiat. Biol., 1990, vol. 57: pp. 97-101.
Billen D. The role of hydroxyl radical scavengers in preventing DNA strand breaks induced by X irradiation of toluene-treated E. coli. Radiat. Res. 1984, vol. 97: pp. 626-629.
Mozdarani H. and Gharbali A. Radioprotective effects of Cimetidine in mouse bone marrow cells exposed to gamma rays as assayed by the micronucleus test. Int. J. Radiat. Biol. 1993, vol. 64: pp. 189-194.
Lapenna D., DEgioia S. et al. H2 receptor antagonists are scavengers of oxygen radicals. Exp. J. Clin. Invest. 1994, vol. 24: pp. 479-481.
Ching T.L., Haenen G.R.M.M. et al. Cimetidine and other H2 receptor antagonists as powerful hydroxyl radical scavengers. Chem. Biol. Interact. 1993, vol. 86: pp. 119–127.
Ching T.L., Jong J.D. et al. Structural characteristics of histamine H2 receptor antagonists that scavenge hypochlorous acid. Eur. J. Pharm. 1994, vol. 268: pp. 89-93.
Heddle J.A., Cimino M.C. et al. Micronuclei as index of cytogenetic damage: past, present and future. Environ. Mol. Mutagen. 1991, vol. 18: pp. 277-91.
Jenssen D. and Ramel C. The micronucleus test as part of a short-term mutagenicity test program for the prediction of carcinogenicity evaluated by 143 agents tested. Mutat. Res., 1980, vol. 75: pp. 191-202.
Shahidi M, and Mozdarani H. Potent radio protective effect of therapeutic doses of ranitidine and famotidine against gamma-ray induced micronuclei in vivo. Iran. J. Radiation Research 2003, vol. 1 (1): pp. 29-35.