DNA Çift Zincir Kırıklarına Neden Olan Fiziksel, Kimyasal ve Biyolojik Ajanlar

Year 2015, Issue: 2, 131 - 145, 01.06.2015

Didem Oral Belma Koçer-gümüşel Pınar Erkekoğlu

Abstract

Endojen ve ekzojen birçok etkene bağlı olarak DNA’da farklı hasarlar oluşabilir. DNA hasarlarının en tehlikelisi ise DNA çift sarmal kırıkları double strand breaks, DSB ’dır. DSB onarımı normalde iki farklı yolla gerçekleştirilir. Ancak, bu onarım yolaklarında meydana gelen herhangi bir bozukluk kanser, yaşlanma ve birçok genetik hastalığa yol açabilir. Fiziksel, kimyasal ve biyolojik ajanların indüklediği reaktif oksijen türleri ROS DSB’na neden olan başlıca etkenlerdir. İyonize radyasyon da dolaylı yolla canlı dokuda yoğun olarak bulunan su molekülüyle etkileşerek oksidatif strese, ROS ve ardından DSB oluşumuna neden olmaktadır. Çevresel veya tedavi amaçlı maruz kalınan pek çok kimyasal ajan ya da ilacın antikanser ajanlar, ağır metaller, asbest, ftalatlar, benzen, okratoksin A gibi da DSB’ye neden olduğu yapılan pekçok çalışma ile gösterilmiştir. Diğer taraftan, insanda gastrit ve ülsere neden olan bir bakteri olan Helicobacter pylori’nin de DSB oluşumu üzerine etkileriyle ilgili çalışmalar devam etmektedir. Ayrıca pek çok bakteri toksinin de DSB’ye neden olabileceği bildirilmiştir. Bu derleme kapsamında DSB’e neden olan fiziksel, kimyasal ve biyolojik ajanlar ve etki mekanizmaları tartışılacaktır.

Keywords

DNA çift sarmal kırıkları, iyonize edici radyasyon, Helicobacter pylori, oksidatif stres

Physical, chemical and biological agents that cause DNA double strand breaks

Abstract

Endogenous and exogenous factors can cause different types of DNA damages. The most dangerous DNA damage is double strand break DSB . Under normal conditions, DSB repair is substantiated by two different mechanisms. However, any disruption in these repair pathways can cause cancer, aging and different types of genetic disorders. Reactive oxygen species ROS induced by physical, chemical and biological agents are the main causes that lead to the formation of DSBs. In living tissues, ionized radiation can interact with water molecules and can cause oxidative stress and formation of ROS and DSB, respectively. Several chemical agents or drugs that humans are exposed to, by environment or therapy anticancer drugs, heavy metals, asbestos, phthalates, benzene, ochratoxin A , were shown to cause DSB by several studies. Research on DSB causing effects of Helicobacter pylori, a bacterium that causes gastritis and ulcer in humans, is still in progress. In addition, several bacterial toxins were stated to cause DSB. This review will mainly focus on agents that cause DSB and their mechanisms of action.

Keywords

DNA double strand breaks, ionized radiation, Helicobacter pylori, oxidative stress

References

• Hoeijmakers, J.H.: DNA damage, aging, and cancer. N Engl J Med ,361,1475 (2009)
• Keith, A.R., Bailey, J.K, Whitham, T.G.: A genetic basis to community repeatability and stability. Ecology, 91, 3398 (2010)
• Esteller, M.: Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum Mol Genet, 16 ,50 (2007)
• Lindahl, T.: Instability and decay of the primary structure of DNA. Nature, 362, 709 (1993)
• Sander, M., Cadet, J., Casciano, D.A., Galloway, S.M., Marnett, L.J., Novak, R.F., Pettit, S.D., Preston, R.J., Skare, J.A., Williams, G.M., Van Houten, B., Gollapudi, B.B.: Proceedings of a workshop on DNA adducts: biological significance and applications to risk assessment Washington, DC. Toxicol Appl Pharmacol. 208, 1 (2005)
• Lemaître, C., Soutoglou, E.: Double strand break (DSB) repair in heterochromatin and heterochromatin proteins in DSB repair. DNA Repair, 19,163 (2014)
• Bush, S.P., Hart, P.E., Russell, E.M.: Investigating DNA Damage. The American Biology Teacher, 68,280 (2006)
• Elia, M.C., DeLuca, J.G., Bradley, M.O.: Significance and measurement of DNA double strand breaks in mammalian cells. Pharmacol Ther, 51,291 (1991)
• Vamvakas, S., Vock, E.H., Lutz, W.K.: On the role of DNA double-strand breaks in toxicity and carcinogenesis. Crit Rev Toxicol, 27,155 (1997)
• Aguilera, A., Gaillard, H. :Transcription and recombination: when RNA meets DNA. Cold Spring Harb Perspect Biol , 6, doi:10.1101/cshperspect.a01654
• Hamperl, S., Cimprich, K.A.: The contribution of co-transcriptional RNA:DNA hybrid structures to DNA damage and genome instability. DNA Repair, 19,84 (2014)
• McCabe, E.R. :Role of mitochondria in oncogenesis. Biochem Med Metab Biol, 47,105(1992)
• Sczepanski, J.T., Jacobs, A.C., Van Houten, B, Greenberg, M.M.: Double-strand break formation during nucleotide excision repair of a DNA interstrand cross-link. Biochemistry, 48, 7565 (2009)
• Kozmin, S.G., Sedletska, Y., Reynaud-Angelin, A., Gasparutto, D., Sage, E.: The formation of double-strand breaks at multiply damaged sites is driven by the kinetics of excision/ incision at base damage in eukaryotic cells. Nucleic Acids Res, 37, 1767 (2009)
• Barnard, S., Bouffler, S., Rothkamm, K.: The shape of the radiation dose response for DNA double-strand break induction and repair. Genome Integr ,4, 1 (2013)
• Cadet, J., Ravanat, J.L., TavernaPorro, M., Menoni, H., Angelov, D.: Oxidatively generated complex DNA damage: tandem and clustered lesions. Cancer Lett, 327, 5 (2012)
• Yamaguchi, H., Uchihori, Y., Yasuda, N., Takada, M., Kitamura, H.: Estimation of yields of OH radicals in water irradiated by ionizing radiation. J Radiat Res, 46, 333 (2005)
• Cannan, W.J, Pederson, D.S.: Mechanisms and Consequences of Double-strand DNA Break Formation in Chromatin. J Cell Physiol, doi:10.1002/jcp.25048 (2015)
• Povirk, L.F.: DNA damage and mutagenesis by radiomimetic DNA-cleaving agents: bleomycin, neocarzinostatin and other enediynes. Mutat Res ,355,71 (1996)
• Anderson, R.D., Berger, N.A.: International Commission for Protection Against Environmental Mutagens and Carcinogens. Mutagenicity and carcinogenicity of topoisomerase-interactive agents. Mutat Res ,309,109 (1994)
• Patel, E., Reynolds, M.: Methylmercury impairs motor function in early development and induces oxidative stress in cerebellar granule cells. Toxicol Lett, 222,265 (2013)
• Ondovcik, S.L., Tamblyn, L., McPherson, J.P., Wells, P.G.: Oxoguanine glycosylase 1(OGG1) protects cells from DNA double-strand break damage following methylmercury (MeHg) exposure. Toxicol Sci, 128,272 (2012)
• Kryeziu, K., Jungwirth, U., Hoda, M.A., Ferk, F., Knasmüller, S., Karnthaler-Benbakka, C., Kowol, C.R., Berger, W., Heffeter, P.: Synergistic anticancer activity of arsenic trioxide with erlotinib is based on inhibition of EGFR-mediated DNA double-strand break repair. Mol Cancer Ther, 12, 1073 (2013)
• Xie, H., Huang, S., Martin, S., Wise, J.P. Sr.: Arsenic is cytotoxic and genotoxic to primary human lung cells. Mutat Res Genet Toxicol Environ Mutagen, 760,33(2014)
• Jiang, L., Nagai, H., Ohara, H., Hara, S., Tachibana M., Hirano S., Shinohara Y., Kohyama N., Akatsuka S., Toyokuni S.: Characteristics and modifying factors of asbestos-induced oxidative DNA damage. Cancer Sci, 99, 2142 (2008)
• Msiska, Z., Pacurari, M., Mishra, A., Leonard, S.S., Castranova, V., Vallyathan, V.: DNA double-strand breaks by asbestos, silica, and titanium dioxide: possible biomarker of carcinogenic potential? Am J Respir Cell Mol Biol, 43, 210 (2010)
• Okayasu, R., Takahashi S., Yamada S., Hei T.K., Ullrich R.L.: Asbestos and DNA double strand breaks. Cancer Res, 59, 298 (1999)
• Marczynski, B., Czuppon, A.B., Marek, W., Reichel, G., Baur, X.: Increased incidence of DNA double-strand breaks and anti-ds DNA antibodies in blood of workers occupationally exposed to asbestos. Hum Exp Toxicol, 13, 3 (1994)
• Lau, A., Belanger, C.L., Winn, L.M.: In utero and acute exposure to benzene: investigation of DNA double-strand breaks and DNA recombination in mice. Mutat Res, 676, 74 (2009)
• Hartwig A.: The role of DNA repair in benzene-induced carcinogenesis. Chem Biol Interact, 184,269 (2010)
• Albro P.W., Lavenhar S.R.: Metabolism of di(2-ethylhexyl)phthalate. Drug Metab Rev,21,13 (1989)
• Erkekoglu, P., Kocer-Gumusel, B.: Genotoxicity of phthalates. Toxicol Mech Methods, 24,(2014)
• Erkekoglu, P., Zeybek, N.D., Giray, B.K., Rachidi, W., Kızılgün, M., Hininger-Favier, I., Favier, A., Asan, E., Hincal, F.: The effects of di(2-ethylhexyl)phthalate on rat liver in relation to selenium status. Int J Exp Pathol, 95, 64 (2014)
• Pogribny, I.P., Tryndyak, V.P., Boureiko, A., Melnyk, S., Bagnyukova, T.V., Montgomery, B., Rusyn, I.: Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liver. Mutat Res. 644, 17 (2008)
• Erkekoglu, P., Rachidi, W., Yuzugullu, O.G., Giray, B., Favier, A., Ozturk, M., Hincal, F.: Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium. Toxicol Appl Pharmacol, 248, 52 (2010)
• Erkekoğlu, P., Rachidi, W., De Rosa, V., Giray, B., Favier, A., Hincal, F.: Protective effect of selenium supplementation on the genotoxicity of di(2-ethylhexyl)phthalate and mono(2- ethylhexyl)phthalate treatment in LNCaP cells. Free Radic Biol Med, 49, 559 (2010)
• Caldwell, J.C.: DEHP: genotoxicity and potential carcinogenic mechanisms-a review. Mutat Res, 751, 82 (2012)
• Wang X., Jiang L., Ge L., Chen M., Yang G., Ji F., Zhong L., Guan Y., Liu X.: Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line. Environ Toxicol Pharmacol, 39,1099 (2015)
• Slator, C., Barron, N., Howe, O., Kellett ,A. [Cu(o-phthalate)(phenanthroline)] exhibits unique superoxide-mediated NCI-60 chemotherapeutic action through genomic DNA damage and mitochondrial dysfunction. ACS Chem Biol, Oct (2015).
• Visagie, C.M, Varga J., Houbraken, J., Meijer, M., Kocsubé, S., Yilmaz, N., Fotedar, R., Seifert, K.A., Frisvad, J.C., Samson, R.A.: Ochratoxin production and taxonomy of the yellow aspergilli (Aspergillus section Circumdati). Stud Mycol, 78,1 (2014)
• Palabiyik, S.S., Erkekoglu, P., Zeybek, N.D., Kizilgun, M., Baydar, D.E., Sahin, G., Giray, B.K.: Protective effect of lycopene against ochratoxin A induced renal oxidative stress and apoptosis in rats. Exp Toxicol Pathol, 65, 853 (2013)
• Ochratoxin A. (Group 2B). International Agency for Research on Cancer (IARC) - Summaries & Evaluations. 5. Summary of Data Reported and Evaluation. İnternet Adresi: http://www. inchem.org/documents/iarc/vol56/13-ochra.html. Erişim Tarihi: 30.7.2015.
• Aydin, S., Palabiyik, S.S., Erkekoglu, P., Sahin, G., Başaran, N., Giray, B.K.: The carotenoid lycopene protects rats against DNA damage induced by Ochratoxin A. Toxicon. 73, 96 (2013)
• Kuroda, K., Hibi, D., Ishii, Y., Takasu, S., Kijima, A., Matsushita, K., Masumura, K., Watanabe, M., Sugita-Konishi, Y., Sakai, H., Yanai, T., Nohmi, T., Ogawa, K., Umemura, T.: Ochratoxin A induces DNA double-strand breaks and large deletion mutations in the carcinogenic target site of gpt delta rats. Mutagenesis, 29, 27 (2014)
• Sedelnikova, O.A., Redon, C.E., Dickey, J.S., Nakamura, A.J., Georgakilas, A.G., Bonner, W.M.: Role of oxidatively induced DNA lesions in human pathogenesis. Mutat Res 704, 152 (2010)
• Machado, A.M., Figueiredo, C., Seruca, R., Rasmussen, L.J. :Helicobacter pylori infection generates genetic instability in gastric cells. Biochim Biophys Acta , 1806, 58 (2010)
• Hanada, K., Uchida, T., Tsukamoto, Y., Watada, M., Yamaguchi, N., Yamamoto, K., Shiota, S., Moriyama, M., Graham, D.Y., Yamaoka, Y.: Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect Immun, 82, 4182 (2014)
• Toller, I.M., Neelsen, K.J., Steger, M, Hartung, M.L., Hottiger, M.O., Stucki, M., Kalali, B., Gerhard, M., Sartori, A.A., Lopes, M., Müller, A.: Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand breaks and a DNA damage response its host cells. Proc Natl Acad Sci U S A, 108,14944 (2011)
• Han, Y.M., Park, J.M., Jeong, M., Yoo, J.H., Kim, W.H., Shin, S.P., Ko, W.J., Hahm, K.B. Dietary, non-microbial intervention to prevent Helicobacter pylori-associated gastric diseases. Ann Transl Med, 3, 122 (2015)
• Elsen S., Collin-Faure V., Gidrol X., Lemercier C.: The opportunistic pathogen Pseudomonas aeruginosa activates the DNA double-strand break signaling and repair pathway in infected cells. Cell Mol Life Sci, 70,4385 (2013)
• Lemercier C.: When our genome is targeted by pathogenic bacteria. Cell Mol Life Sci,72,2665 (2015)
• Lai, C.H., Chang, C.S., Liu, H.H., Tsai, Y.S., Hsu, F.M., Yu, Y.L., Lai, C.K., Gandee, L., Pong, R.C., Hsu, H.W., Yu, L., Saha, D., Hsieh, J.T. Sensitization of radio-resistant prostate cancer cells with a unique cytolethal distending toxin. Oncotarget, 5, 5523 (2014)
• Li, L., Sharipo, A., Chaves-Olarte, E., Masucci, M.G., Levitsky, V., Thelesltalm, M., Frisan, T.: The Haemophilus ducreyi cytolethal distending toxin activates sensors of DNA damage and repair complexes in proliferating and non-proliferating cells. Cell. Microbiol.: 4,87(2002)
• Frisan, T., Cortes-Bratti, X., Chaves-Olarte, E., Stenerlöw, B., Thelestam, M.: The Haemophilus ducreyi cytolethal distending toxin induces DNA double-strand breaks and promotes ATM-dependent activation of RhoA. Cell Microbiol, 10,695(2003)
• Chumduri, C., Gurumurthy, R.K., Zadora, P.K., Mi, Y., Meyer, T.F.: Chlamydia infection promotes host DNA damage and proliferation but impairs the DNA damage response.Cell Host Microbe, 13,746 (2013)
• Hsieh Y.H., Chang Y.Y., Su I.J., Yen C.J., Liu Y.R., Liu RJ, Hsieh W.C., Tsai H.W., Wang L.H., Huang W. : Hepatitis B virus pre-S2 mutant large surface protein inhibits DNA double- strand break repair and leads to genome instability in hepatocarcinogenesis. J Pathol, 236,337 (2015)
• Wang X., Jiang L., Ge L., Chen M., Yang G., Ji F., Zhong L., Guan Y., Liu X.: Oxidative DNA damage induced by di-(2-ethylhexyl) phthalate in HEK-293 cell line. Environ Toxicol Pharmacol, 39,1099 (2015)
• Kennedy, R.D., D’Andrea A.D. DNA Repair Pathways in Clinical Practice: Lessons From Pediatric Cancer Susceptibility Syndromes. J Clin Oncol, 24, 3799 (2006)