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Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi

Year 2019, Volume: 14 Issue: 1, 29 - 37, 28.04.2019
https://doi.org/10.17094/ataunivbd.387311

Abstract

Hepatoselüler karsinom (HCC) karaciğer hücrelerinden köken kansere bağlı ölümlerde de üçüncü sırada yer alan malign kanser türüdür. Parietin genellikle ışkın (Rheum ribes L.) gibi bazı bitkilerden izole edilen bir antrakinondur. Sitotoksik ve genotoksik testler karsinojenik ve kalıtımsal risklerin değerlendirilmesinde önemli testlerdir. Bu çalışmada parietinin HepG2 hepatoselüler karsinom hücrelerinde sitotoksik ve genotoksik etkisinin araştırılması amaçlanmıştır. HepG2 hücreleri uygun koşullarda kültüre edildi. Daha sonra hücrelere 25-1000 μM aralığında konsantrasyonda parietin uygulanarak 24-48 saat inkübasyona bırakıldı. Hücre canlılık oranı XTT yöntemi ile doza ve zamana bağlı olarak belirlendi. Genototoksik etkisi ise komet yöntemi ile belirlendi. Elde edilen veriler istatiksel olarak değerlendirildi. Parietinin HepG2 hücrelerine IC50 değeri 48. saatte 25 μM olarak belirlendi. Komet analiz sonuçlarına göre DNA kuyruk uzunluğu, kuyruk yoğunluğu ve kuyruk momenti gibi parametrelerde istatistiksel olarak anlamlı bir artış görülmedi (p>0.05). Bu çalışmada, parietinin HepG2 hücrelerinde düşük konsantrasyonda sitotoksik etki gösterdiği fakat genotoksik etki göstermediği gösterilmiştir. Sonuç olarak parietin, hepatoselüler karsinom tedavisinde diğer ilaçlarla birlikte kombine olarak faydalı bir ajan olabileceği öngörülmekle birlikte ve yapılacak olan daha detaylı çalışmalarla da desteklenmelidir. 

References

  • 1. Kutluk T., Kars A., Kanser konusunda güncel Bilgiler. T.C. Sağlık Bakanlığı Sağlık Projesi Genel Koordinatörlüğü Kanser ve Savaş Daire Başkanlığı, Ankara.2. WHO, 2017. Guide to cancer early diagnosis. World Health Organization Document Production Services, Geneva, Switzerland.3. IARC, 2014. Bernard WS, Chistoper PW. World Cancer Report, 630, ISBN-13 9789283204299.4. Merlo LM., Pepper JW., Reid BJ., Maley CC., 2006. Cancer as an Evolutionary and Ecological Process. Nat Rev Cancer, 6, 924-935.5. Guyton AC., Hall JE., 2001. Protein Sentezi, Hücre Fonksiyonu ve Hücre Çoğalmasinin Genetik Kontrolü. In “Tıbbi Fizyoloji”, Ed., H Çavuşcuoğlu, 10th ed., 24-37, Nobel Tıp Kitapevleri Ltd Şti, Ankara.6. Hanahan D., Weinberg RA., 2011. Hallmarks of Cancer: The Next Generation. Cell, 144(5), 646-674.7. Lodish H., Berk A., Kaiser CA., Krieger M., Scott MP., Bretscher A., Ploeg H., Matsudaira P., 2008. Molecular Cell Biology. 6th. Edititon. 1107-1108, W.H.Freeman and Company, New York.8. Türker FA., Kayaalp SO., 2002. Kanser Kemoterapisinin Esasları ve Antineoplastik Ilaçlar. 380-415, Feryal Matbaacılık, Ankara.9. Tozkoparan B., Aytaç SP., 2007. Kanser Kemoterapisinde Terapötik Hedef Olarak Gluatatyon S-Transferazlar. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 27, 139-164.10. Roy-byrne PP., Bystritsky A., Russo J., Craske MG., Sherbourne CD., Stein MB., 2005. Use of Herbal Medicine in Primary Care Patients with Mood and Anxiety Disorders. Psychosomatics, 46, 117–122.11. Steinmetz KA., Potter JD., 1991. Vegetables, Fruit, and Cancer. II. Mechanisms. Cancer Causes Control, 2(6), 427-42.12. Ziegler RG., Colavito EA., Hartge P., McAdams MJ., Schoenberg JB., Mason TJ., Fraumeni JF., 1996. Importance of alpha-carotene, beta-carotene, and other Phytochemicals in The Etiology of Lung Cancer. Natl Cancer Inst, 9, 612-5.13. Jemal A., Bray F., Center MM., Ferlay J., Ward E., Forman D., 2011. Global cancer statistics. Cancer Journal of Clinicians, 61 (2), 69–90.14. Athar M., Back JH., Tang X., Kim KH., Kopelovich L., Bickers DR., Kim AL., 2007. Resveratrol: A Review of Preclinical Studies for Human Cancer Prevention. Toxicology and Applied Pharmacology, 224 (3), 274-83.15. Venugopal R., Liu RH., 2012. Phytochemicals in Diets For Breast Cancer Prevention: The Importance of Resveratrol and Ursolic Acid. Food Science and Human Wellness, 1 (1), 1-13.16. Singh CK., George J., Ahmad N., 2013. Resveratrol-based Combinatorial Strategies for Cancer Management. Annals of the New York Academy of Science, 1290, 113-21.17. Kojiro M., Roskams T., 2005. Early Hepatocellular Carcinoma and Dysplastic Nodules. Seminars in Liver Disease, 25, 133-142.18. Villanueva A., Newell P., Chiang DY., Friedman SL., Llovet JM., 2007. Genomics and Signaling Pathways in Hepatocellular Carcinoma. Seminars in Liver Disease, 27, 55-76.19. Shibata S., Ukita T., Tamura T., Miura Y., 1948. Relation between Chemical Constitutions and Antibacterial Effects of Usnic Acid and Derivatives. Jap Med J, 1, 152–55.20. Özenoğlu S., Aydoğdu G., Dinçsoy AB., Taghidizaj AA., Derici K., Yılmaz E., Aras S., Cansaran-Duman D., 2013. Liken Sekonder Bileşiklerinin Farklı Insan Kanser Hücre Tipleri Üzerine Antikanserojenik Etkisi. Turk Hij Den Biyol Derg, 70(4), 215-26.21. Asahina Y., 1967. Lichenologische Notizen. J Jap Bot, 42, 289-94.22. Huneck S., Yoshimura I., 1996. Identification of Lichen Substances. Berlin. Springer, 304- 49.23. Miao V., Legal MFC., Brown D., Sinnemann S., Donaldson G., Davies J., 2001. Genetic Approaches to Harvesting Lichen Products. Trends in Biotechnol, 19, 349-355.24. Şekerli M., Kılıç N., Cansaran-Duman D., 2017. Liken Metabolitlerinin Antikanser Aktivite Etkisinin Moleküler Düzeydeki Mekanizmaları. Turk Hij Dern Biyol Derg, 74(1), 95-10225. Comini L., Vieyra FEM., Mignone RA., Páez PL., Mugas ML., Konigheim BS., Cabrera JL., Montoya SCN., Borsarelli CD., 2017. Parietin: an efficient photo-screening pigment in vivo with good photosensitizing and photodynamic antibacterial effects in vitro. Photochem Photobiol Sci, 16(2), 201-210.26. Solhaug K., Gauslaa Y., 1996. Parietin, a Photoprotective Secondary Product of the Lichen Xanthoria Parietina, Oecologia, 108, 412–418.27. Gauslaa Y., Ustvedt EM., 2003. Is Parietin a UV-B or a Blue-Light Screening Pigment in The Lichen Xanthoria Parietina?. Photochem Photobiol Sci, 2, 424–432.28. Bačkorová M., Jendželovský R., Kello M., 2012. Lichen Secondary Metabolites are Responsible for Induction of Apoptosis In HT-29 and A2780 Human Cancer Cell Lines. Toxicol in Vitro, 26, 462-8.29. Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S., Conte B., Paoli L., De Ruberto F., Molinari AM., Altucci L., Bontempo P., 2015. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin. Int J Mol Sci, 16, 7861– 7875.30. Gibellini L., Pinti M., Nasi M., Montagna JP., Biasi SD., Roat E., Bertoncelli L., Cooper EL., Cossarizza A., 2011. Quercetin and Cancer Chemoprevention. Evidence-Based Complementary and Alternative Medicine, 1-15.31. Viskupicova J., Ondrejovic M., Sturdik E., 2008. Bioavailability And Metabolism Of Flavonoids. J Food Nutr Res, 47(4), 151–162.32. Mitrović T., Stamenković S., Cvetković V., Tošić S., Stanković M., Radojević I., Stefanović O., Comić L., Daćić D., Curćić M., Marković S., 2011. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species. Int J Mol Sci, 12, 5428-48. 33. Brisdelli F., Perilli M., Sellitri D., 2013. Cytotoxic Activity and Antioxidant Capacity of Purified Lichen Metabolites: an in Vitro Study. Phytother Res, 27, 431-7.34. Singh N., Nambiar D., Kale RK., Singh RP., 2013. Usnic Acid Inhibits Growth and Induces Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma A549 Cells. Nutr Cancer, 65, 36-43.35. Russo A., Caggia S., Piovano M., 2012. Effect of Vicanicin and On Human Prostate Cancer Cells: Role of Hsp70 Protein. Chem Biol Interact, 195, 1-10.36. Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S, Conte B., Paoli L., De Ruberto F., Molinari AM., Altucci L., Bontempo P., 2015. .Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin. Int J Mol Sci, 16(4), 7861-75. 37. Triggiani D., Ceccarelli D., Tiezzi A., Pisani T., Munzi S., Gaggi C., Loppi S., 2009. Antiproliferative Activity of Lichen Extracts on Murine Myeloma Cells. Biologia, 64, 59–62.38. Backorova M., Backor M., Mikes J., Jendzelovsky R., Fedorocko P., 2011. Variable Responses of Different Human Cancer Cells to the Lichen Compounds Parietin, Atranorin, Usnic Acid and Gyrophoric Acid. Toxicol In Vitro, 25, 37–44.39. Kim H., Keun Kim K., Hur JS., 2015. Anticancer activity of lichen metabolites and their mechanisms at the molecular level. In “Recent Advances in Lichenology”, Ed. DK Upreti. 201-8, Springer, India.

Determination of Cytotoxic and Genotoxic Effects of Parietin in HepG2 Hepatocellular Carcinoma Cells

Year 2019, Volume: 14 Issue: 1, 29 - 37, 28.04.2019
https://doi.org/10.17094/ataunivbd.387311

Abstract

Hepatocellular carcinoma (HCC) originating from liver cells is the third leading cause of cancer-related death. Parietin is an anthraquinone, isolated from some plants such as Rheum ribes L. Cytotoxicity and genotoxicity tests have an important role in the assessment of heritable and carcinogenic risks. In this study, it was aimed to investigate the cytotoxic and genotoxic effect of parietin on HepG2 hepatocellular carcinoma cells. HepG2 cells were cultured in appropriate culture medium. Then, different concentrations of parietin (final concentrations in the well to be 25-1000 μM) were added to the cells and they were allowed to incubate for 24-48 hours. Cell viability and genotoxic effect were determined by using XTT method and comet assay, respectively. The IC50 concentration of parietin was detected as 25 μM at the 48 hour in HepG2 cells. According to the comet assay, there was no statistically significant increase DNA tail length, DNA tail intensity and DNA tail moment in parietin treated cell groups compared to control groups (p>0.05). In this study, it has been shown that parietin has cytotoxic at low dose, but has not genotoxic effect in HepG2 cells, and as a result parietin was found to be useful in combination with other drugs in the treatment of HepG2 cells. However, this effect of parietin should be supported by further studies.

References

  • 1. Kutluk T., Kars A., Kanser konusunda güncel Bilgiler. T.C. Sağlık Bakanlığı Sağlık Projesi Genel Koordinatörlüğü Kanser ve Savaş Daire Başkanlığı, Ankara.2. WHO, 2017. Guide to cancer early diagnosis. World Health Organization Document Production Services, Geneva, Switzerland.3. IARC, 2014. Bernard WS, Chistoper PW. World Cancer Report, 630, ISBN-13 9789283204299.4. Merlo LM., Pepper JW., Reid BJ., Maley CC., 2006. Cancer as an Evolutionary and Ecological Process. Nat Rev Cancer, 6, 924-935.5. Guyton AC., Hall JE., 2001. Protein Sentezi, Hücre Fonksiyonu ve Hücre Çoğalmasinin Genetik Kontrolü. In “Tıbbi Fizyoloji”, Ed., H Çavuşcuoğlu, 10th ed., 24-37, Nobel Tıp Kitapevleri Ltd Şti, Ankara.6. Hanahan D., Weinberg RA., 2011. Hallmarks of Cancer: The Next Generation. Cell, 144(5), 646-674.7. Lodish H., Berk A., Kaiser CA., Krieger M., Scott MP., Bretscher A., Ploeg H., Matsudaira P., 2008. Molecular Cell Biology. 6th. Edititon. 1107-1108, W.H.Freeman and Company, New York.8. Türker FA., Kayaalp SO., 2002. Kanser Kemoterapisinin Esasları ve Antineoplastik Ilaçlar. 380-415, Feryal Matbaacılık, Ankara.9. Tozkoparan B., Aytaç SP., 2007. Kanser Kemoterapisinde Terapötik Hedef Olarak Gluatatyon S-Transferazlar. Hacettepe Üniversitesi Eczacılık Fakültesi Dergisi, 27, 139-164.10. Roy-byrne PP., Bystritsky A., Russo J., Craske MG., Sherbourne CD., Stein MB., 2005. Use of Herbal Medicine in Primary Care Patients with Mood and Anxiety Disorders. Psychosomatics, 46, 117–122.11. Steinmetz KA., Potter JD., 1991. Vegetables, Fruit, and Cancer. II. Mechanisms. Cancer Causes Control, 2(6), 427-42.12. Ziegler RG., Colavito EA., Hartge P., McAdams MJ., Schoenberg JB., Mason TJ., Fraumeni JF., 1996. Importance of alpha-carotene, beta-carotene, and other Phytochemicals in The Etiology of Lung Cancer. Natl Cancer Inst, 9, 612-5.13. Jemal A., Bray F., Center MM., Ferlay J., Ward E., Forman D., 2011. Global cancer statistics. Cancer Journal of Clinicians, 61 (2), 69–90.14. Athar M., Back JH., Tang X., Kim KH., Kopelovich L., Bickers DR., Kim AL., 2007. Resveratrol: A Review of Preclinical Studies for Human Cancer Prevention. Toxicology and Applied Pharmacology, 224 (3), 274-83.15. Venugopal R., Liu RH., 2012. Phytochemicals in Diets For Breast Cancer Prevention: The Importance of Resveratrol and Ursolic Acid. Food Science and Human Wellness, 1 (1), 1-13.16. Singh CK., George J., Ahmad N., 2013. Resveratrol-based Combinatorial Strategies for Cancer Management. Annals of the New York Academy of Science, 1290, 113-21.17. Kojiro M., Roskams T., 2005. Early Hepatocellular Carcinoma and Dysplastic Nodules. Seminars in Liver Disease, 25, 133-142.18. Villanueva A., Newell P., Chiang DY., Friedman SL., Llovet JM., 2007. Genomics and Signaling Pathways in Hepatocellular Carcinoma. Seminars in Liver Disease, 27, 55-76.19. Shibata S., Ukita T., Tamura T., Miura Y., 1948. Relation between Chemical Constitutions and Antibacterial Effects of Usnic Acid and Derivatives. Jap Med J, 1, 152–55.20. Özenoğlu S., Aydoğdu G., Dinçsoy AB., Taghidizaj AA., Derici K., Yılmaz E., Aras S., Cansaran-Duman D., 2013. Liken Sekonder Bileşiklerinin Farklı Insan Kanser Hücre Tipleri Üzerine Antikanserojenik Etkisi. Turk Hij Den Biyol Derg, 70(4), 215-26.21. Asahina Y., 1967. Lichenologische Notizen. J Jap Bot, 42, 289-94.22. Huneck S., Yoshimura I., 1996. Identification of Lichen Substances. Berlin. Springer, 304- 49.23. Miao V., Legal MFC., Brown D., Sinnemann S., Donaldson G., Davies J., 2001. Genetic Approaches to Harvesting Lichen Products. Trends in Biotechnol, 19, 349-355.24. Şekerli M., Kılıç N., Cansaran-Duman D., 2017. Liken Metabolitlerinin Antikanser Aktivite Etkisinin Moleküler Düzeydeki Mekanizmaları. Turk Hij Dern Biyol Derg, 74(1), 95-10225. Comini L., Vieyra FEM., Mignone RA., Páez PL., Mugas ML., Konigheim BS., Cabrera JL., Montoya SCN., Borsarelli CD., 2017. Parietin: an efficient photo-screening pigment in vivo with good photosensitizing and photodynamic antibacterial effects in vitro. Photochem Photobiol Sci, 16(2), 201-210.26. Solhaug K., Gauslaa Y., 1996. Parietin, a Photoprotective Secondary Product of the Lichen Xanthoria Parietina, Oecologia, 108, 412–418.27. Gauslaa Y., Ustvedt EM., 2003. Is Parietin a UV-B or a Blue-Light Screening Pigment in The Lichen Xanthoria Parietina?. Photochem Photobiol Sci, 2, 424–432.28. Bačkorová M., Jendželovský R., Kello M., 2012. Lichen Secondary Metabolites are Responsible for Induction of Apoptosis In HT-29 and A2780 Human Cancer Cell Lines. Toxicol in Vitro, 26, 462-8.29. Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S., Conte B., Paoli L., De Ruberto F., Molinari AM., Altucci L., Bontempo P., 2015. Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin. Int J Mol Sci, 16, 7861– 7875.30. Gibellini L., Pinti M., Nasi M., Montagna JP., Biasi SD., Roat E., Bertoncelli L., Cooper EL., Cossarizza A., 2011. Quercetin and Cancer Chemoprevention. Evidence-Based Complementary and Alternative Medicine, 1-15.31. Viskupicova J., Ondrejovic M., Sturdik E., 2008. Bioavailability And Metabolism Of Flavonoids. J Food Nutr Res, 47(4), 151–162.32. Mitrović T., Stamenković S., Cvetković V., Tošić S., Stanković M., Radojević I., Stefanović O., Comić L., Daćić D., Curćić M., Marković S., 2011. Antioxidant, Antimicrobial and Antiproliferative Activities of Five Lichen Species. Int J Mol Sci, 12, 5428-48. 33. Brisdelli F., Perilli M., Sellitri D., 2013. Cytotoxic Activity and Antioxidant Capacity of Purified Lichen Metabolites: an in Vitro Study. Phytother Res, 27, 431-7.34. Singh N., Nambiar D., Kale RK., Singh RP., 2013. Usnic Acid Inhibits Growth and Induces Cell Cycle Arrest and Apoptosis in Human Lung Carcinoma A549 Cells. Nutr Cancer, 65, 36-43.35. Russo A., Caggia S., Piovano M., 2012. Effect of Vicanicin and On Human Prostate Cancer Cells: Role of Hsp70 Protein. Chem Biol Interact, 195, 1-10.36. Basile A., Rigano D., Loppi S., Di Santi A., Nebbioso A., Sorbo S, Conte B., Paoli L., De Ruberto F., Molinari AM., Altucci L., Bontempo P., 2015. .Antiproliferative, Antibacterial and Antifungal Activity of the Lichen Xanthoria parietina and Its Secondary Metabolite Parietin. Int J Mol Sci, 16(4), 7861-75. 37. Triggiani D., Ceccarelli D., Tiezzi A., Pisani T., Munzi S., Gaggi C., Loppi S., 2009. Antiproliferative Activity of Lichen Extracts on Murine Myeloma Cells. Biologia, 64, 59–62.38. Backorova M., Backor M., Mikes J., Jendzelovsky R., Fedorocko P., 2011. Variable Responses of Different Human Cancer Cells to the Lichen Compounds Parietin, Atranorin, Usnic Acid and Gyrophoric Acid. Toxicol In Vitro, 25, 37–44.39. Kim H., Keun Kim K., Hur JS., 2015. Anticancer activity of lichen metabolites and their mechanisms at the molecular level. In “Recent Advances in Lichenology”, Ed. DK Upreti. 201-8, Springer, India.
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Details

Primary Language Turkish
Subjects Health Care Administration
Journal Section Araştırma Makaleleri
Authors

Alper Kürşat Demirkaya

Gülşah Gündoğdu

Yavuz Dodurga

Mücahit Seçme

Köksal Gündoğdu This is me

Publication Date April 28, 2019
Published in Issue Year 2019 Volume: 14 Issue: 1

Cite

APA Demirkaya, A. K., Gündoğdu, G., Dodurga, Y., Seçme, M., et al. (2019). Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, 14(1), 29-37. https://doi.org/10.17094/ataunivbd.387311
AMA Demirkaya AK, Gündoğdu G, Dodurga Y, Seçme M, Gündoğdu K. Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. April 2019;14(1):29-37. doi:10.17094/ataunivbd.387311
Chicago Demirkaya, Alper Kürşat, Gülşah Gündoğdu, Yavuz Dodurga, Mücahit Seçme, and Köksal Gündoğdu. “Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik Ve Genotoksik Etkisinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 14, no. 1 (April 2019): 29-37. https://doi.org/10.17094/ataunivbd.387311.
EndNote Demirkaya AK, Gündoğdu G, Dodurga Y, Seçme M, Gündoğdu K (April 1, 2019) Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 14 1 29–37.
IEEE A. K. Demirkaya, G. Gündoğdu, Y. Dodurga, M. Seçme, and K. Gündoğdu, “Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi”, Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 14, no. 1, pp. 29–37, 2019, doi: 10.17094/ataunivbd.387311.
ISNAD Demirkaya, Alper Kürşat et al. “Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik Ve Genotoksik Etkisinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi 14/1 (April 2019), 29-37. https://doi.org/10.17094/ataunivbd.387311.
JAMA Demirkaya AK, Gündoğdu G, Dodurga Y, Seçme M, Gündoğdu K. Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2019;14:29–37.
MLA Demirkaya, Alper Kürşat et al. “Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik Ve Genotoksik Etkisinin Belirlenmesi”. Atatürk Üniversitesi Veteriner Bilimleri Dergisi, vol. 14, no. 1, 2019, pp. 29-37, doi:10.17094/ataunivbd.387311.
Vancouver Demirkaya AK, Gündoğdu G, Dodurga Y, Seçme M, Gündoğdu K. Parietinin HepG2 Hepatoselüler Karsinom Hücrelerinde Sitotoksik ve Genotoksik Etkisinin Belirlenmesi. Atatürk Üniversitesi Veteriner Bilimleri Dergisi. 2019;14(1):29-37.