Analysis of Genotoxic Damage in Different Diseases

Yıl 2021, Cilt: 3 Sayı: 2, 124 - 132, 25.08.2021

Gülşen Göney Nurhan Halisdemir

Öz

Aim: Research has revealed that diseases changed the repair mechanism of DNA chain breaks. Recent studies indicate that genomic instability results in cancer. The present study aimed to assess the association between diseases and DNA damage measured with the comet assay in humans.
Method: In a cross-sectional study the level of genotoxic damage was evaluated in peripheral blood samples by simple random sampling method in Turkish adults using Single Cell Gel Electrophoresis assay. The results of possible DNA damage levels of disease groups were compared with the results of healthy people. A p-value of less than 0.01 was considered as statistically significant.
Results: 128 (52 women and 76 men) participated in the study. The tail moment was 1.39±1.21 in healthy groups and 1.41±0.91 in patient groups. Our result showed that participants with hepatitis, thyroid dysfunctions, and psychiatric diseases had statistically significant differences in DNA damage compared to healthy ones.
Conclusion and Suggestions: Our findings suggest that patients with hepatitis, thyroid dysfunctions, and psychiatric diseases are at risk of genotoxic damage. Genotoxicity tests have gained importance in early biomonitoring of cancer. Therefore, the relationship between diseases and cancer development should be investigated with different genotoxic experiments.

Anahtar Kelimeler

Comet Assay, DNA Damage, Genotoxicity, Disease, Single Cell Gel Electrophoresis.

Farklı Hastalıklarda Genotoksik Hasarın Analizi

Öz

Amaç: Son yıllarda yapılmış olan araştırmalar ile obezitenin, DNA zincir kırıklarının onarım mekanizmasını değiştirdiği ortaya çıkartılmıştır. Ayrıca Beden Kitle indeksinde artış ile genomik kararsızlık arasında ilişki tespit edilmiştir. Sunulan çalışmada farklı hastalık gruplarındaki bireylerde muhtemel genotoksik hasarının araştırılması amaçlanmıştır.
Yöntem: Sunulan çalışmada 18 yaşından büyük aşırı kilolu ya da normal kiloya sahip bireylerin periferal lenfositlerinde olası DNA hasarı comet deneyi ile analiz edilmiştir. Farklı hastalık gruplarındaki kişilere ait olası DNA hasar düzeyi sonuçları kontrol grubunu oluşturan sağlıklı kişilerin sonuçları ile SPSS analiz programı kullanılarak istatistiksel olarak karşılaştırılmıştır.
Bulgular: Sunulan araştırmaya yaş ortalaması 33,60±10,80 olan 52 kadın, 76 erkek 128 gönüllü katılmıştır. Sağlıklı bireylerden oluşan kontrol grubunda kuyruk momenti değeri 1.39±1.21 olarak tespit edilirken bu değer hastalığa sahip bireylerin oluşturduğu grupta 1.41±0.91 olarak tespit edilmiştir. Hastalık ve kontrol grubunda Kuyruk momenti değeri sonuçları karşılaştırıldığında tiroid ve hepatit hastalarında istatsitiksel oarak anlamlı fark bulunmuştıur (p<0.01). Sonuçlarımız hastalıkların DNA hasarını etkileyebileceğini göstermektedir.
Sonuç ve Öneriler: Sunulan çalışma Türkiye’deki hastalığa sahip yetişkin bireylerde hastalık tipi ve DNA hasar düzeyinin değerlendirildiği ilk çalışma olma özelliğindedir. Gelecekte hastalık ve DNA hasar düzeyi ilişkisinin genotoksisite testleriyle araştırılacağı yeni çalışmaların yapılması önerilmektedir.

Anahtar Kelimeler

Comet deneyi, DNA hasarı, Genotoksisite, Hastalık, Tek tek hücre jel elektroforezi

Kaynakça

• Møller, P., Stopper, H., & Collins, A. R. (2020). Measurement of DNA damage with the comet assay in high-prevalence diseases: current status and future directions. Mutagenesis, 35(1), 5-18.
• Blasiak, J., Arabski, M., Krupa, R., Wozniak, K., Zadrozny, M., Kasznicki, J., ... & Drzewoski, J. (2004). DNA damage and repair in type 2 diabetes mellitus. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 554(1-2), 297-304.
• Ibarra-Costilla, E., Cerda-Flores, R. M., Dávila-Rodríguez, M. I., Samayo-Reyes, A., Calzado-Flores, C., & Cortés-Gutiérrez, E. I. (2010). DNA damage evaluated by comet assay in Mexican patients with type 2 diabetes mellitus. Acta diabetologica, 47(1), 111-116.
• Botto, N., Masetti, S., Petrozzi, L., Vassalle, C., Manfredi, S., Biagini, A., & Andreassi, M. G. (2002). Elevated levels of oxidative DNA damage in patients with coronary artery disease. Coronary artery disease, 13(5), 269-274.
• Demirbag, R., Yilmaz, R., & Kocyigit, A. (2005). Relationship between DNA damage, total antioxidant capacity and coronary artery disease. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 570(2), 197-203.
• Gerić, M., Domijan, A. M., Gluščić, V., Janušić, R., Šarčević, B., & Garaj-Vrhovac, V. (2016). Cytogenetic status and oxidative stress parameters in patients with thyroid diseases. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 810, 22-29.
• Poplawski, T., Chojnacki, C., Czubatka, A., Klupinska, G., Chojnacki, J., & Blasiak, J. (2013). Helicobacter pylori infection and antioxidants can modulate the genotoxic effects of heterocyclic amines in gastric mucosa cells. Molecular biology reports, 40(8), 5205-5212.
• Ladeira, M. S., Rodrigues, M. A., Freire-Maia, D. V., & Salvadori, D. M. (2005). Use of Comet assay to assess DNA damage in patients infected by Helicobacter pylori: comparisons between visual and image analyses. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 586(1), 76-86.
• Zeyrek, D., Cakmak, A., Atas, A., Kocyigit, A., & Erel, O. (2009). DNA damage in children with asthma bronchiale and its association with oxidative and antioxidative measurements. Pediatric allergy and immunology, 20(4), 370-376.
• Hasbal, C., Aksu, B. Y., Himmetoglu, S., Dincer, Y., Koc, E. E., Hatipoglu, S., & Akcay, T. (2010). DNA damage and glutathione level in children with asthma bronchiale: effect of antiasthmatic therapy. Pediatric Allergy and Immunology, 21(4p2), e674-e678.
• Horoz, M., Bolukbas, C., Bolukbas, F. F., Kocyigit, A., Aslan, M., Koylu, A. O., ... & Koksal, M. (2006). Assessment of peripheral DNA damage by alkaline comet assay in maintenance hemodialysis subjects with hepatitis C infection. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 596(1-2), 137-142.
• Bolukbas, C., Bolukbas, F. F., Kocyigit, A., Aslan, M., Selek, S., Bitiren, M., & Ulukanligil, M. (2006). Relationship between levels of DNA damage in lymphocytes and histopathological severity of chronic hepatitis C and various clinical forms of hepatitis B. Journal of gastroenterology and hepatology, 21(3), 610-616.
• Esteves, F., Teixeira, E., Amorim, T., Costa, C., Pereira, C., Fraga, S., ... & Costa, S. (2017). Assessment of DNA damage in a group of professional dancers during a 10-month dancing season. Journal of Toxicology and Environmental Health, Part A, 80(13-15), 797-804.
• Andreazza, A. C., Frey, B. N., Erdtmann, B., Salvador, M., Rombaldi, F., Santin, A., ... & Kapczinski, F. (2007). DNA damage in bipolar disorder. Psychiatry research, 153(1), 27-32.
• Czarny, P., Kwiatkowski, D., Kacperska, D., Kawczyńska, D., Talarowska, M., Orzechowska, A., ... & Śliwiński, T. (2015). Elevated level of DNA damage and impaired repair of oxidative DNA damage in patients with recurrent depressive disorder.
• Tice, R. R., Agurell, E., Anderson, D., Burlinson, B., Hartmann, A., Kobayashi, H., ... & Sasaki, Y. F. (2000). Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environmental and molecular mutagenesis, 35(3), 206-221.
• Nelson, B. C., & Dizdaroglu, M. (2020). Implications of DNA damage and DNA repair on human diseases. Mutagenesis, 35(1), 1-3.
• Jackson, S. P., & Bartek, J. (2009). The DNA-damage response in human biology and disease. Nature, 461(7267), 1071-1078.
• Dearfield, K. L., Cimino, M. C., McCarroll, N. E., Mauer, I., & Valcovic, L. R. (2002). Genotoxicity risk assessment: a proposed classification strategy. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 521(1-2), 121-135.
• Mohamed, S. A. K. S., Upreti, S., Rajendra, S. V., & Dang, R. (2017). Genotoxicity: mechanisms, testing guidelines and methods. Global Journal of Pharmacy & Pharmaceutical Sciences, 1(5), 133-138.
• Mamur, S., Unal, F., Altok, K., Deger, S. M., & Yuzbasioglu, D. (2016). DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 800, 22-27.
• Pitozzi, V., Giovannelli, L., Bardini, G., Rotella, C. M., & Dolara, P. (2003). Oxidative DNA damage in peripheral blood cells in type 2 diabetes mellitus: higher vulnerability of polymorphonuclear leukocytes. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 529(1-2), 129-133.
• Anderson, D., Yu, T. W., Wright, J., & Ioannides, C. (1998). An examination of DNA strand breakage in the comet assay and antioxidant capacity in diabetic patients. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 398(1-2), 151-161.
• Botto, N., Masetti, S., Petrozzi, L., Vassalle, C., Manfredi, S., Biagini, A., & Andreassi, M. G. (2002). Elevated levels of oxidative DNA damage in patients with coronary artery disease. Coronary artery disease, 13(5), 269-274.
• Bhat, M. A., & Gandhi, G. (2017). Assessment of DNA damage in leukocytes of patients with coronary artery disease by comet assay. International heart journal, 58(2), 271-274.
• Leprat, F., Alapetite, C., Rosselli, F., Ridet, A., Schlumberger, M., Sarasin, A., & Moustacchi, E. (1998). Impaired DNA repair as assessed by the “comet” assay in patients with thyroid tumors after a history of radiation therapy: a preliminary study. International Journal of Radiation Oncology Biology Physics, 40(5), 1019-1026.
• Fujita, N., Sugimoto, R., Ma, N., Tanaka, H., Iwasa, M., Kobayashi, Y., ... & Takei, Y. (2008). Comparison of hepatic oxidative DNA damage in patients with chronic hepatitis B and C. Journal of viral hepatitis, 15(7), 498-507.
• Mikhailov, A. O., Popov, A. F., Ivanova, N. S., & Simakova, A. I. (2017). The investigation of DNA damage in lymphocytes by comet assay in chronic viral hepatitis B patients. Epidemiology and Infectious Diseases, 22(2), 64-68.