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Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes

Yıl 2023, Cilt: 6 Sayı: 4, 540 - 549, 15.10.2023
https://doi.org/10.34248/bsengineering.1340985

Öz

Analgesics are one of the most widely used drug groups in the world. Since the genotoxic and carcinogenic effects of some analgesic drugs have been detected, studies investigating these effects have increased. In this study, the genotoxic effects of the analgesic drugs Tenoxicam and Piroxicam were investigated in vitro in human peripheral lymphocytes by chromosomal aberrations (CAs) and micronucleus (MN) assays. In addition, mitotic index (MI) and nuclear division index (NDI) values were also determined. As a result, no difference in chromosomal abnormalities was observed in both 24 and 48 hours of Piroxicam treatment. Micronucleus frequency was increased at the three highest concentrations (0.94, 1.88 and 3.75 µg/mL) compared to the control. Piroxicam significantly decreased MI compared to both control and solvent control at concentrations of 1.88 and 3.75 µg/mL at all exposure times. Tenoxicam showed a statistically significant increase at the highest concentration (10 μg/mL) compared to the control in the 24 h CA treatment. On the other hand, no effect was observed in 48-hour CA treatment. It was concluded that tenoxicam did not cause a toxic effect at any concentration except the highest concentration (10 μg/mL) in the MN assay results. Mitotic index (MI) significantly decreased at concentrations of 1.25, 2.5, 5 and 10 μg/mL. Nuclear division index (NDI) results did not change for both agents. In conclusion, both agents were found to be genotoxic only at high concentrations and the effect was weak. This study is pioneering as there have been no previous in vitro studies in human peripheral lymphocytes for both Piroxicam and Tenoxicam. These results need to be supported by different cell groups and in vivo assays.

Kaynakça

  • Ali KA, Maity A, Roy SD, Pramanik SD, Das PP, Shaharyar MA. 2023. Insight into the mechanism of steroidal and non-steroidal anti-inflammatory drugs. In: Kazmi I, Karmakar S, Shaharyar A, Afzal M, Al Abbasi FA, editors. How synthetic drugs work. Academic Press, Cambridge, Massachusetts, USA, pp: 61-94.
  • Alonso-Jauregui M, López de Cerain A, Azqueta A, Rodriguez-Garraus A, Gil AG, González-Peñas E, Vettorazzi A. 2023. In vivo genotoxicity and toxicity assessment of sterigmatocystin ındividually and in mixture with aflatoxin B1. Toxins, 15(8): 491.
  • Bagatir G, Kaya M, Suer I, Cefle K, Palanduz A, Palanduz S, Becerir EB, Kocyigit M, Ozturk S. 2022. The effect of anzer honey on X‐ray induced genotoxicity in human lymphocytes: an in vitro study. Microsc Res Tech, 85(6): 2241-2250.
  • Balkaya AN, Kaya FN, Filiz TA, Karaca U. 2021. Postoperatif ağrı kontrolünde preemptif ve postoperatif tek doz tenoksikam uygulamasının etkinliğinin karşılaştırılması. BUÜTF Dergisi, 47(1): 97-104.
  • Becker DE, Phero JC. 2005. Drug therapy in dental practice: nonopioid and opioid analgesics. Anesth Prog, 52:140- 149.
  • Bhattacharya SK. 2000. Antioxidant activity of bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res, 14 (3): 174–179.
  • Bindu S, Mazumder S, Bandyopadhyay U. 2020. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol, 180: 114147.
  • Bonassi S, El-Zein R, Bolognesi C, Fenech M. 2011. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis, 26(1): 93-100.
  • Brammilla G, Martelli A. 2009. Genotoxicity and carcinogenicity studies of analgesics, anti-inflammatory drugs and antipyretics. Pharmacol Res, 60: 1-17.
  • Chiong HS, Yong YK, Ahmad Z, Sulaiman MR, Zakaria ZA, Yuen KH, Hakim MN. 2013. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages. Int J Nanomedicine, 8: 1245-1255.
  • Choy WN. 2001. Genetic toxicology and cancer risk assessment. First edition, CRC Press, New York, USA, pp: 29-47.
  • da Silva JCG, Dallegrave E, Rodrigues GZP, Bigolin C, Neumann TMSDO, Schuster AC, et al. 2022. Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice. Drug Chemical Toxicol, 45(2): 822-833.
  • Dkhil MA, Tohamy A, Gabry MS. 2011. Chromosomal aberrations induced in bone marrow cells of mice due to the administration of the non-steroidal anti-inflammatory drug, Piroxicam. Afr J Pharm Pharmacol, 5(1): 98-103.
  • Ellwanger JH, Kulmann-Leal B, Ziliotto M, Chies JAB. 2023. HIV Infection, chromosome instability, and micronucleus formation. Viruses, 15(1): 155.
  • El-Zein R, Vral A, Etzel CJ. 2011. Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis, 26(1): 101–106.
  • Evans HJ, (1984) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. In: Kilbey B J, Legator M, Nichols W, Ramel C editors, Handbook of mutagenicity test procedures, Elsevier Sciences, Amsterdam, pp: 405–424.
  • Ewing LE, Pathak R, Landes RD, Skinner CM, Binz R, Young SG, et al. 2023. Cytogenetic and epigenetic aberrations in peripheral lymphocytes of northwest Arkansas Marshallese. Int J Radiat Biol, 99(4): 644-655.
  • Fenech M. 2000. The in vitro micronucleus technique. Mutat Res, 455: 81-95.
  • Fenech M. 1993. The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. Environ Health Perspect, 101(3): 101-107.
  • Fernandes E, Toste SA, Lima JL, Reis S. 2003. The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species. Free Radic Biol Med, 35(9):1008-1017.
  • Hagmar L, Strömberg U, Bonassi S, Hansteen IL, Knudsen LE, Lindholm C, Norppa H. 2004. Impact of types of lymphocyte chromosomal aberrations on human cancer risk results from nordic and italian cohorts. Cancer Res, 64(6): 2258-2263.
  • Harding AP, Popelier PL, Harvey J, Giddings A, Foster G, Kranz M. 2015. Evaluation of aromatic amines with different purities and different solvent vehicles in the Ames test. Regul Toxicol Pharmacol, 71(2): 244-250.
  • Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F. 2003. IgE- mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. Journal Allergy Clin Immunol, 111: 882-888.
  • Ila, H. B., and Husunet, M.T. 2022. Kromozom anormallikleri testi. In: Unal F, Yuzbasioglu D, editors. Genetik Toksikoloji, Ankara, Palme; 2022:153-179.
  • Islami A, Sopyan I, Gozali D, Hairunnisa H. 2020. Revıew Modıfıkası Kelarutan Pıroksıkam. Jurnal Ilmiah Farmako Bahari, 11(1): 89-102.
  • Jain AK, Sorbhoy RK.1988. Cytogenetical studies on the effects of some chlorinated pesticides. Cytologia, 53: 427-436.
  • Kılıc M, Tuylu BA. 2020. An in vitro investigation of genotoxic effects of dexketoprofen trometamol on healthy human lymphocytes. Drug Chem Toxicol, 43(2): 174-181.
  • Kishino Y, Hasegawa T, Yamoto T, Mori K. 2019. Species differences in micronucleus induction of the clastogenic compounds associated with drug metabolic profile. J Toxicol Sci, 44(10): 701-709.
  • Kullich W, Klein G. 1986. Investigations of the influence of nonsteroidal antirheumatic drugs on the rates of sister-chromatid exchange. Mutat Res Lett, 174(2): 131-134.
  • Mamur S, Ataseven N, Ünal F, Yüzbaşıoğlu D. 2018. Gıdalarda koruyucu katkı maddesi olarak kullanılan sodyum benzoat ve potasyum sorbat karışımının genotoksik eşiğin mikronükleus testi ile belirlenmesi. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 20 (2): 235-245.
  • Mirza S, Miroshnyk I, Habib MJ, Brausch JF, Hussain MD. 2010. Enhanced dissolution and oral bioavailability of piroxicam formulations: modulating effect of phospholipids. Pharmaceutics, 2(4): 339-350.
  • Natarajan A T, Boei JJWA. 2003. Formation of chromosome aberrations: insights from FISH. Mutat Res, 544(2): 299-304.
  • Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, et al. 2006. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res, 600(1-2): 37-45.
  • Organization for Economic Co-operation and Development (OECD) 2016a. Test No. 473: In Vitro Mammalian Chromosomal Aberration Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264264649-en
  • Organization for Economic Co-operation and Development (OECD) 2016b. Test No. 487: In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264264861-en
  • Organization for Economic Co-operation and Development (OECD), 2008. OECD Guidelines for the Testing of Chemicals, Health Effects, 4: 471–486
  • Pandey KB, Rizvi SI, 2010. Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid Med Cell Longev, 3(1): 2–12.
  • Raj SG, Rajitha V. 2023. Assessment of genotoxic instability markers in peripheral blood lymphocytes of breast cancer patients: a case control study. J Biomol Struct Dyn, 2023: 1-5.
  • Rina T, Shyam SP, Pankaj T. 2012. Genotoxicity of ibuprofen in mouse bone marrow cells in vivo. Drug and Chem Toxicol, 27: 940-951.
  • Riss TL, Moravec RA. 2004. Use of multiple assay endpoints to investigate the effects of incubation time, dose of toxin and plating density in cell-based cytotoxicity assays. Assay Drug Dev Technol, 2(1): 51- 62.
  • Sherif M, Makame KR, Östlundh L, Paulo MS, Nemmar A, Ali BR, et al. 2023. Genotoxicity of occupational pesticide exposures among agricultural workers in arab countries: a systematic review and meta-analysis. Toxics, 11(8): 663.
  • Shohin IE, Kulinich JI, Ramenskaya GV, Abrahamsson B, Kopp S, Langguth P, et al. 2014. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam. J Pharm Sci, 103(2): 367-377.
  • Siivola KK, Burgum MJ, Suárez-Merino B, Clift MJ, Doak SH, Catalán J. 2022. A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective. Part Fibre Toxicol, 19(1): 1-24.
  • Takebayashi K, Echizenya K, Kameya Y, et al. 2023. Mitotic index maximization with no effect on radiation-induced dicentric chromosome frequency. Int J Radiat Biol, 99(5):750-759.
  • Timoroglu İ, Yuzbasioglu D, Unal F, Yilmaz S, Aksoy H, Celik M. 2014. Assessment of the genotoxic effects of organophosphorus insecticides phorate and trichlorfon in human lymphocytes. Environ toxicol, 29(5): 577-587.
  • Ustuner D. 2011. Kromozom kırıkları ve mikronükleus-apoptoz bağlantısı. TÜBAV Bilim Dergisi, 4(1): 64-69.
  • Van’t Hof J. 1968. The action of iaa and kinetin on the mitotic cycle of proliferative and stationary phase excised root meristems. Exp Cell Res, 51(1): 167-176.
  • Yilmaz I, Tutar N, Yenigun S, Ozer Simsek Z, Gulmez I. 2017. Tenoxicam-induced fixed drug eruption confirmed by skin patch test. Asthma Allergy Immunol, 15(3): 162-164.
  • Yuzbasioglu D, Celik M, Yilmaz S, Unal F, Aksoy H. 2006. Clastogenicity of the fungicide afugan in cultured human lymphocytes. Mutat Res, 604: 53-59.
  • Yuzbasioglu D, Avuloglu-Yilmaz E. Mikronükleus testi. In: Unal F, Yuzbasioglu D, editors. Genetik Toksikoloji, Ankara, Palme; 2022: 219-249.

Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes

Yıl 2023, Cilt: 6 Sayı: 4, 540 - 549, 15.10.2023
https://doi.org/10.34248/bsengineering.1340985

Öz

Analgesics are one of the most widely used drug groups in the world. Since the genotoxic and carcinogenic effects of some analgesic drugs have been detected, studies investigating these effects have increased. In this study, the genotoxic effects of the analgesic drugs Tenoxicam and Piroxicam were investigated in vitro in human peripheral lymphocytes by chromosomal aberrations (CAs) and micronucleus (MN) assays. In addition, mitotic index (MI) and nuclear division index (NDI) values were also determined. As a result, no difference in chromosomal abnormalities was observed in both 24 and 48 hours of Piroxicam treatment. Micronucleus frequency was increased at the three highest concentrations (0.94, 1.88 and 3.75 µg/mL) compared to the control. Piroxicam significantly decreased MI compared to both control and solvent control at concentrations of 1.88 and 3.75 µg/mL at all exposure times. Tenoxicam showed a statistically significant increase at the highest concentration (10 μg/mL) compared to the control in the 24 h CA treatment. On the other hand, no effect was observed in 48-hour CA treatment. It was concluded that tenoxicam did not cause a toxic effect at any concentration except the highest concentration (10 μg/mL) in the MN assay results. Mitotic index (MI) significantly decreased at concentrations of 1.25, 2.5, 5 and 10 μg/mL. Nuclear division index (NDI) results did not change for both agents. In conclusion, both agents were found to be genotoxic only at high concentrations and the effect was weak. This study is pioneering as there have been no previous in vitro studies in human peripheral lymphocytes for both Piroxicam and Tenoxicam. These results need to be supported by different cell groups and in vivo assays.

Kaynakça

  • Ali KA, Maity A, Roy SD, Pramanik SD, Das PP, Shaharyar MA. 2023. Insight into the mechanism of steroidal and non-steroidal anti-inflammatory drugs. In: Kazmi I, Karmakar S, Shaharyar A, Afzal M, Al Abbasi FA, editors. How synthetic drugs work. Academic Press, Cambridge, Massachusetts, USA, pp: 61-94.
  • Alonso-Jauregui M, López de Cerain A, Azqueta A, Rodriguez-Garraus A, Gil AG, González-Peñas E, Vettorazzi A. 2023. In vivo genotoxicity and toxicity assessment of sterigmatocystin ındividually and in mixture with aflatoxin B1. Toxins, 15(8): 491.
  • Bagatir G, Kaya M, Suer I, Cefle K, Palanduz A, Palanduz S, Becerir EB, Kocyigit M, Ozturk S. 2022. The effect of anzer honey on X‐ray induced genotoxicity in human lymphocytes: an in vitro study. Microsc Res Tech, 85(6): 2241-2250.
  • Balkaya AN, Kaya FN, Filiz TA, Karaca U. 2021. Postoperatif ağrı kontrolünde preemptif ve postoperatif tek doz tenoksikam uygulamasının etkinliğinin karşılaştırılması. BUÜTF Dergisi, 47(1): 97-104.
  • Becker DE, Phero JC. 2005. Drug therapy in dental practice: nonopioid and opioid analgesics. Anesth Prog, 52:140- 149.
  • Bhattacharya SK. 2000. Antioxidant activity of bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res, 14 (3): 174–179.
  • Bindu S, Mazumder S, Bandyopadhyay U. 2020. Non-steroidal anti-inflammatory drugs (NSAIDs) and organ damage: a current perspective. Biochem Pharmacol, 180: 114147.
  • Bonassi S, El-Zein R, Bolognesi C, Fenech M. 2011. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis, 26(1): 93-100.
  • Brammilla G, Martelli A. 2009. Genotoxicity and carcinogenicity studies of analgesics, anti-inflammatory drugs and antipyretics. Pharmacol Res, 60: 1-17.
  • Chiong HS, Yong YK, Ahmad Z, Sulaiman MR, Zakaria ZA, Yuen KH, Hakim MN. 2013. Cytoprotective and enhanced anti-inflammatory activities of liposomal piroxicam formulation in lipopolysaccharide-stimulated RAW 264.7 macrophages. Int J Nanomedicine, 8: 1245-1255.
  • Choy WN. 2001. Genetic toxicology and cancer risk assessment. First edition, CRC Press, New York, USA, pp: 29-47.
  • da Silva JCG, Dallegrave E, Rodrigues GZP, Bigolin C, Neumann TMSDO, Schuster AC, et al. 2022. Repeated dose of meloxicam induces genotoxicity and histopathological changes in cardiac tissue of mice. Drug Chemical Toxicol, 45(2): 822-833.
  • Dkhil MA, Tohamy A, Gabry MS. 2011. Chromosomal aberrations induced in bone marrow cells of mice due to the administration of the non-steroidal anti-inflammatory drug, Piroxicam. Afr J Pharm Pharmacol, 5(1): 98-103.
  • Ellwanger JH, Kulmann-Leal B, Ziliotto M, Chies JAB. 2023. HIV Infection, chromosome instability, and micronucleus formation. Viruses, 15(1): 155.
  • El-Zein R, Vral A, Etzel CJ. 2011. Cytokinesis-blocked micronucleus assay and cancer risk assessment. Mutagenesis, 26(1): 101–106.
  • Evans HJ, (1984) Human peripheral blood lymphocytes for the analysis of chromosome aberrations in mutagen tests. In: Kilbey B J, Legator M, Nichols W, Ramel C editors, Handbook of mutagenicity test procedures, Elsevier Sciences, Amsterdam, pp: 405–424.
  • Ewing LE, Pathak R, Landes RD, Skinner CM, Binz R, Young SG, et al. 2023. Cytogenetic and epigenetic aberrations in peripheral lymphocytes of northwest Arkansas Marshallese. Int J Radiat Biol, 99(4): 644-655.
  • Fenech M. 2000. The in vitro micronucleus technique. Mutat Res, 455: 81-95.
  • Fenech M. 1993. The cytokinesis-block micronucleus technique and its application to genotoxicity studies in human populations. Environ Health Perspect, 101(3): 101-107.
  • Fernandes E, Toste SA, Lima JL, Reis S. 2003. The metabolism of sulindac enhances its scavenging activity against reactive oxygen and nitrogen species. Free Radic Biol Med, 35(9):1008-1017.
  • Hagmar L, Strömberg U, Bonassi S, Hansteen IL, Knudsen LE, Lindholm C, Norppa H. 2004. Impact of types of lymphocyte chromosomal aberrations on human cancer risk results from nordic and italian cohorts. Cancer Res, 64(6): 2258-2263.
  • Harding AP, Popelier PL, Harvey J, Giddings A, Foster G, Kranz M. 2015. Evaluation of aromatic amines with different purities and different solvent vehicles in the Ames test. Regul Toxicol Pharmacol, 71(2): 244-250.
  • Himly M, Jahn-Schmid B, Pittertschatscher K, Bohle B, Grubmayr K, Ferreira F. 2003. IgE- mediated immediate-type hypersensitivity to the pyrazolone drug propyphenazone. Journal Allergy Clin Immunol, 111: 882-888.
  • Ila, H. B., and Husunet, M.T. 2022. Kromozom anormallikleri testi. In: Unal F, Yuzbasioglu D, editors. Genetik Toksikoloji, Ankara, Palme; 2022:153-179.
  • Islami A, Sopyan I, Gozali D, Hairunnisa H. 2020. Revıew Modıfıkası Kelarutan Pıroksıkam. Jurnal Ilmiah Farmako Bahari, 11(1): 89-102.
  • Jain AK, Sorbhoy RK.1988. Cytogenetical studies on the effects of some chlorinated pesticides. Cytologia, 53: 427-436.
  • Kılıc M, Tuylu BA. 2020. An in vitro investigation of genotoxic effects of dexketoprofen trometamol on healthy human lymphocytes. Drug Chem Toxicol, 43(2): 174-181.
  • Kishino Y, Hasegawa T, Yamoto T, Mori K. 2019. Species differences in micronucleus induction of the clastogenic compounds associated with drug metabolic profile. J Toxicol Sci, 44(10): 701-709.
  • Kullich W, Klein G. 1986. Investigations of the influence of nonsteroidal antirheumatic drugs on the rates of sister-chromatid exchange. Mutat Res Lett, 174(2): 131-134.
  • Mamur S, Ataseven N, Ünal F, Yüzbaşıoğlu D. 2018. Gıdalarda koruyucu katkı maddesi olarak kullanılan sodyum benzoat ve potasyum sorbat karışımının genotoksik eşiğin mikronükleus testi ile belirlenmesi. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 20 (2): 235-245.
  • Mirza S, Miroshnyk I, Habib MJ, Brausch JF, Hussain MD. 2010. Enhanced dissolution and oral bioavailability of piroxicam formulations: modulating effect of phospholipids. Pharmaceutics, 2(4): 339-350.
  • Natarajan A T, Boei JJWA. 2003. Formation of chromosome aberrations: insights from FISH. Mutat Res, 544(2): 299-304.
  • Norppa H, Bonassi S, Hansteen IL, Hagmar L, Strömberg U, Rössner P, et al. 2006. Chromosomal aberrations and SCEs as biomarkers of cancer risk. Mutat Res, 600(1-2): 37-45.
  • Organization for Economic Co-operation and Development (OECD) 2016a. Test No. 473: In Vitro Mammalian Chromosomal Aberration Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264264649-en
  • Organization for Economic Co-operation and Development (OECD) 2016b. Test No. 487: In Vitro Mammalian Cell Micronucleus Test, OECD Guidelines for the Testing of Chemicals, Section 4, OECD Publishing, Paris, https://doi.org/10.1787/9789264264861-en
  • Organization for Economic Co-operation and Development (OECD), 2008. OECD Guidelines for the Testing of Chemicals, Health Effects, 4: 471–486
  • Pandey KB, Rizvi SI, 2010. Markers of oxidative stress in erythrocytes and plasma during aging in humans. Oxid Med Cell Longev, 3(1): 2–12.
  • Raj SG, Rajitha V. 2023. Assessment of genotoxic instability markers in peripheral blood lymphocytes of breast cancer patients: a case control study. J Biomol Struct Dyn, 2023: 1-5.
  • Rina T, Shyam SP, Pankaj T. 2012. Genotoxicity of ibuprofen in mouse bone marrow cells in vivo. Drug and Chem Toxicol, 27: 940-951.
  • Riss TL, Moravec RA. 2004. Use of multiple assay endpoints to investigate the effects of incubation time, dose of toxin and plating density in cell-based cytotoxicity assays. Assay Drug Dev Technol, 2(1): 51- 62.
  • Sherif M, Makame KR, Östlundh L, Paulo MS, Nemmar A, Ali BR, et al. 2023. Genotoxicity of occupational pesticide exposures among agricultural workers in arab countries: a systematic review and meta-analysis. Toxics, 11(8): 663.
  • Shohin IE, Kulinich JI, Ramenskaya GV, Abrahamsson B, Kopp S, Langguth P, et al. 2014. Biowaiver monographs for immediate release solid oral dosage forms: piroxicam. J Pharm Sci, 103(2): 367-377.
  • Siivola KK, Burgum MJ, Suárez-Merino B, Clift MJ, Doak SH, Catalán J. 2022. A systematic quality evaluation and review of nanomaterial genotoxicity studies: a regulatory perspective. Part Fibre Toxicol, 19(1): 1-24.
  • Takebayashi K, Echizenya K, Kameya Y, et al. 2023. Mitotic index maximization with no effect on radiation-induced dicentric chromosome frequency. Int J Radiat Biol, 99(5):750-759.
  • Timoroglu İ, Yuzbasioglu D, Unal F, Yilmaz S, Aksoy H, Celik M. 2014. Assessment of the genotoxic effects of organophosphorus insecticides phorate and trichlorfon in human lymphocytes. Environ toxicol, 29(5): 577-587.
  • Ustuner D. 2011. Kromozom kırıkları ve mikronükleus-apoptoz bağlantısı. TÜBAV Bilim Dergisi, 4(1): 64-69.
  • Van’t Hof J. 1968. The action of iaa and kinetin on the mitotic cycle of proliferative and stationary phase excised root meristems. Exp Cell Res, 51(1): 167-176.
  • Yilmaz I, Tutar N, Yenigun S, Ozer Simsek Z, Gulmez I. 2017. Tenoxicam-induced fixed drug eruption confirmed by skin patch test. Asthma Allergy Immunol, 15(3): 162-164.
  • Yuzbasioglu D, Celik M, Yilmaz S, Unal F, Aksoy H. 2006. Clastogenicity of the fungicide afugan in cultured human lymphocytes. Mutat Res, 604: 53-59.
  • Yuzbasioglu D, Avuloglu-Yilmaz E. Mikronükleus testi. In: Unal F, Yuzbasioglu D, editors. Genetik Toksikoloji, Ankara, Palme; 2022: 219-249.
Toplam 50 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Genetik (Diğer)
Bölüm Research Articles
Yazarlar

Hümeyra Gül 0000-0001-5258-8051

Ece Avuloğlu Yılmaz 0000-0002-5164-3431

Erken Görünüm Tarihi 4 Ekim 2023
Yayımlanma Tarihi 15 Ekim 2023
Gönderilme Tarihi 10 Ağustos 2023
Kabul Tarihi 29 Eylül 2023
Yayımlandığı Sayı Yıl 2023 Cilt: 6 Sayı: 4

Kaynak Göster

APA Gül, H., & Avuloğlu Yılmaz, E. (2023). Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes. Black Sea Journal of Engineering and Science, 6(4), 540-549. https://doi.org/10.34248/bsengineering.1340985
AMA Gül H, Avuloğlu Yılmaz E. Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes. BSJ Eng. Sci. Ekim 2023;6(4):540-549. doi:10.34248/bsengineering.1340985
Chicago Gül, Hümeyra, ve Ece Avuloğlu Yılmaz. “Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes”. Black Sea Journal of Engineering and Science 6, sy. 4 (Ekim 2023): 540-49. https://doi.org/10.34248/bsengineering.1340985.
EndNote Gül H, Avuloğlu Yılmaz E (01 Ekim 2023) Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes. Black Sea Journal of Engineering and Science 6 4 540–549.
IEEE H. Gül ve E. Avuloğlu Yılmaz, “Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes”, BSJ Eng. Sci., c. 6, sy. 4, ss. 540–549, 2023, doi: 10.34248/bsengineering.1340985.
ISNAD Gül, Hümeyra - Avuloğlu Yılmaz, Ece. “Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes”. Black Sea Journal of Engineering and Science 6/4 (Ekim 2023), 540-549. https://doi.org/10.34248/bsengineering.1340985.
JAMA Gül H, Avuloğlu Yılmaz E. Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes. BSJ Eng. Sci. 2023;6:540–549.
MLA Gül, Hümeyra ve Ece Avuloğlu Yılmaz. “Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes”. Black Sea Journal of Engineering and Science, c. 6, sy. 4, 2023, ss. 540-9, doi:10.34248/bsengineering.1340985.
Vancouver Gül H, Avuloğlu Yılmaz E. Investigation of the Genotoxic Effects of the Analgesic Drugs Piroxicam and Tenoxicam in Human Lymphocytes. BSJ Eng. Sci. 2023;6(4):540-9.

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