Genotoxic and anti-proliferative effects of aminoguanidine on gamma-irradiated MCF-7 breast cancer cells.
DOI:
https://doi.org/10.15392/bjrs.v7i1.788Keywords:
nitric oxide, radiation, breast cancerAbstract
The intracellular production of nitric oxide is studied as a relevant phenomenon in exposure to ionizing radiation. There is evidence of local nitric oxide production in solid tumours. Its effects were observed on the relationship between their presence with tumor progression, linked to the emergence of potential genotoxic or cytotoxic damage, or loss of proliferative capacities of tumour cells. The study evaluated the effects of the administration of aminoguanidine, a selective inhibitor of an isoform of nitric oxide synthase on the frequency of genotoxic damage, loss of clonogenic potential, induction of cytotoxicity and nitrite production after exposure to ionizing radiation in radiotherapeutic doses. Human breast tumor (MCF7) cells were treated with aminoguanidine (1 or 2 mM) and irradiated by gamma radiation at doses between 0.5 and 8Gy. The study used a well stablished technique with some modifications for evaluation of genotoxic damage by frequency of micronuclei in binucleated cells. In cultures treated with 1 mM, we observed increased cytotoxicity and genotoxicity, and reduction of the clonogenic potential of the colonies. Alternatively, 2 mM aminoguanidine produced the opposite effect, apparently protecting cultures from the effects of exposures. The experiments suggested that the administration of aminoguanidine may reduce the in vitro radiossensitivity of tumors due to the increase of the frequency of genotoxic damage.
- Views: 184
- PDF Downloads: 183
Downloads
References
HAN, W., WU, L., CHEN, S., BAO, L., ZHANG, L., JIANG, E., ZHAO, Y., XU, A.,HEI, T. K., YU, Z. Constitutive nitric oxide acting as a possible intercellular signaling molecule in the initiation of radiation-induced DNA double strand breaks in non-irradiated bystander cells. Oncogene.;26(16), p. 2330–9, 2007
BURKE, A.J., SULLIVAN, F.J., GILES, F.J., GLYNN, S.A. The yin and yang of nitric oxide in cancer progression. Carcinogenesis. 34(3), p. 503–12, 2013
KORKMAZ, A., OTER, S., SEYREK, M., TOPAL, T. Molecular, genetic and epigenetic pathways of peroxynitrite-induced cellular toxicity. Interdiscip Toxicol. 2(4), p. 219–28, 2009
MUNTANÉ, J., De la MATA, M. Nitric oxide and cancer. World J Hepatol. 2(9), p. 337–44, 2010
YASUDA, H. Solid tumor physiology and hypoxia-induced chemo/radio-resistance: Novel strategy for cancer therapy: Nitric oxide donor as a therapeutic enhancer. Nitric Oxide - Biol Chem, 19(2), p. 205–16, 2008
FITZPATRICK, B., MEHIBLE, M., COWEN, R.L., STRATFORD, I.J. iNOS as a therapeutic target for treatment of human tumors. Nitric oxide - Biol Chem, 19(2), p. 217–24, 2008
HANAUE, N., TAKEDA, I., KIZU, Y., TONOGI, M., YAMANE, G., ANAUE, N.H., AKEDA, I.T., IZU, Y.K., ONOGI, M.T., AMANE, G.Y. Peroxynitrite formation in radiation-induced salivary gland dysfunction in mice. Biomed Res, 28(3), p. 147–51 2007
WANG, Y., CHEN, C., LOAKE, G.J., CHU, C. Nitric oxide: Promoter or suppressor of programmed cell death? Protein Cell, 1(2), p. 133–42, 2010
ALDERTON, W.K., COOPER, C.E., KNOWLES, R.G. Nitric oxide synthases: structure, function and inhibition. Biochem J, 357(Pt 3), p. 593–615, 2001
WILKES, D.K., De VRIES, A., OLIVER, D.W., MALAN, S.F. Nitric oxide synthase inhibition by pentacycloundecane conjugates of aminoguanidine and tryptamine. Arch Pharm (Weinheim), 342(2), p. 73–9, 2009
MASTUMOTO, H., HAYASHI, S., HATASHITA, M., SHIOURA, H., OHTSUBO, T., KITAI, R., OHNISHI, T., YUKAWA, O., FURUSAWA, Y., KANO, E., Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma. Int J Radiat Biol., 76(12), p. 1649–57, 2000
OHTA, S., MATSUDA, S.M., UNJI, M.G., AMOGAWA, A.K., The role of nitric oxide in radiation damage. Biol Pharm Bull., 30(6), p. 1102–7, 2007
WARDMAN, P., ROTHKAMM, K., FOLKES, L.K., WOODCOCK, M., JOHNSTON, P.J. Radiosensitization by nitric oxide at low radiation doses. Radiat Res, 167(4), p. 475–84, 2007
CAVAŞ, T. In vivo genotoxicity of mercury chloride and lead acetate: Micronucleus test on acridine orange stained fish cells. Food Chem Toxicol, 46(1), p. 352–8, 2008
POLARD, T., JEAN, S., MERLINA, G., LAPLANCHE, C., PINELLI, E., GAUTHIER, L. Giemsa versus acridine orange staining in the fish micronucleus assay and validation for use in water quality monitoring. Ecotoxicol Environ Saf, 74(1), p. 144–9, 2011
SUN, L.P., LI, D.Z., LIU, Z.M., YANG, L.J., LIU, J.Y., CAO, J. Analysis of micronuclei in the transferrin-receptor positive reticulocytes from peripheral blood of nasopharyngeal cancer patients undergoing radiotherapy by a single-laser flow cytometer. J Radiat Res, 46(1), p. 25–35, 2005
HEDDLE, J.A., FENECH, M., HAYASHI, M., MacGREGOR, J.T. Reflections on the development of micronucleus assays. Mutagenesis, 26(1), p. 3–10, 2011
IAEA. Technical reports Series No. 405 - Cytogenetic Analysis for Radiation Dose Assessment: A Manual. 2001;
FENECH, M. Cytokinesis-block micronucleus cytome assay. Nat Protoc, 2(5), p. 1084–104, 2007
SU X, TAKAHASHI, A., GUO, G., MORI, E., OKAMOTO, N., OHNISHI, YUKA-WA, O., FURUSAWA, Y., KANO, E. Biphasic Effects of Nitric Oxide Radicals on Radiation-Induced Lethality and Chromosome Aberrations in Human Lung Cancer Cells Carrying Different p53 Gene Status. Int J Radiat Oncol Biol Phys,77(2), p. 559–65, 2010
ABDELMAGID, S.A., TOO, C.K.L. Prolactin and estrogen up-regulate carboxypeptidase-D to promote nitric oxide production and survival of MCF-7 breast cancer cells. Endocrinology, 149(10), p. 4821–8, 2008
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Brazilian Journal of Radiation Sciences
This work is licensed under a Creative Commons Attribution 4.0 International License.
Licensing: The BJRS articles are licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
