Genotoxic properties of hypoglycemic drugs (systematic review)

Abstract

According to the literature genotoxic properties of about a half of hypoglycemic drugs have not been investigated in accordance with the recommended methodology, and studies of the mutagen-modifying activity of antidiabetic drugs are sporadic. Based on the available published data, it is impossible to conclude about either presence or absence of genotoxic / antigenotoxic potential of antidiabetic drugs. There is evidence of the antimutagenic activity of metformin; in relation to other drugs, studies of mutagen-modifying activity have not been carried out or are represented only by a few articles. Further study of the genotoxic properties of hypoglycemic drugs is required in accordance with modern approaches and requirements, as well as an assessment of their mutagen-modifying activity.

Keywords

diabetes / chromosomal aberrations / micronuclei / DNA comet assay / DNA damage / genotoxicity / antigenotoxicity

References

[1] IDF Guide for Diabetes Epidemiology Studies [Internet] [cited 2021 May 15]. Available from: https://www.idf.org/our-activities/epidemiology-research/idf-guide-for-diabetes-epidemiology-studies.html

[2] IDF Guide for Diabetes Epidemiology Studies [Internet]. Доступ по ссылке: https://www.idf.org/our-activities/epidemiology-research/idf-guide-for-diabetes-epidemiology-studies.html. Дата обращения: 15.05.2021.

[3] Chen L, Magliano DJ, Zimmet PZ. The worldwide epidemiology of type 2 diabetes mellitus – present and future perspectives. Nat Rev Endocrinol. 2011;8(4):228–236. DOI: 10.1038/nrendo.2011.183

[4] Chen L., Magliano D.J., Zimmet P.Z. The worldwide epidemiology of type 2 diabetes mellitus – present and future perspectives // Nat Rev Endocrinol. 2011. Vol. 8. No. 4. P. 228–236. DOI: 10.1038/nrendo.2011.183

[5] Habib SL, Rojna M. Diabetes and risk of cancer. ISRN Oncol. 2013;2013:583786. DOI: 10.1155/2013/583786

[6] Habib S.L., Rojna M. Diabetes and risk of cancer // ISRN Oncol. 2013. Vol. 2013. ID583786. DOI: 10.1155/2013/583786

[7] Barone BB, Yeh HC, Snyder CF, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300(23):2754–2764. DOI: 10.1001/jama.2008.824

[8] Barone B.B., Yeh H.C., Snyder C.F., et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis // JAMA. 2008. Vol. 300. No. 23. P. 2754–2764. DOI: 10.1001/jama.2008.824

[9] Bonassi S, Znaor A, Norppa H, Hagmar L. Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective. Cytogenet Genome Res. 2004;104(1–4):376–382. DOI: 10.1159/000077519

[10] Bonassi S., Znaor A., Norppa H., Hagmar L. Chromosomal aberrations and risk of cancer in humans: an epidemiologic perspective // Cytogenet Genome Res. 2004. Vol. 104. No. 1–4. P. 376–382. DOI: 10.1159/000077519

[11] Bonassi S, El-Zein R, Bolognesi C, Fenech M. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies. Mutagenesis. 2011;26(1):93–100. DOI: 10.1093/mutage/geq075

[12] Bonassi S., El-Zein R., Bolognesi C., Fenech M. Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies // Mutagenesis. 2011. Vol. 26. No. 1. P. 93–100. DOI: 10.1093/mutage/geq075

[13] Eremina NV, Zhanataev AK, Lisitsyn AA, Durnev AD. Genotoxic markers in patients with diabetes mellitus (Literature review). Ecological genetics. 2021;19(2):143–168. (In Russ.) DOI: 10.17816/ecogen65073

[14] Еремина Н.В., Жанатаев А.К., Лисицын А.А., Дурнев А.Д. Генотоксические маркеры у больных сахарным диабетом (обзор литературы) // Экологическая генетика. 2021. Т. 19. № 2. С. 143–168. DOI: 10.17816/ecogen65073

[15] Demirbag R, Yilmaz R, Gur M, et al. DNA damage in metabolic syndrome and its association with antioxidative and oxidative measurements. Int J Clin Pract. 2006;60(10):1187–1193. DOI:10.1111/j.1742-1241.2006.01042.x

[16] Demirbag R., Yilmaz R., Gur M., et al. DNA damage in metabolic syndrome and its association with antioxidative and oxidative measurements // Int J Clin Pract. 2006. Vol. 60. No. 10. P. 1187–1193. DOI: 10.1111/j.1742-1241.2006.01042.x

[17] Balabolkin MI. Rol’ glikirovaniya belkov, okislitel’nogo stressa v patogeneze sosudistykh oslozhnenii pri sakharnom diabete. Diabetes mellitus. 2002;(4):8–16. (In Russ.) DOI: 10.14341/DM200248-16

[18] Балаболкин М.И. Роль гликирования белков, окислительного стресса в патогенезе сосудистых осложнений при сахарном диабете // Сахарный диабет. 2002. № 4. С. 8–16. DOI: 10.14341/DM200248-16

[19] Darenskaya MA, Kolesnikova LI, Kolesnikov SI. Oxidative stress: pathogenetic role in diabetes mellitus and its complications development, therapeutic approaches to correction. Byulleten’ eksperimental’noj biologii i mediciny. 2021;171(2):136–149. (In Russ.) DOI: 10.1007/s10517-021-05191-7

[20] Даренская М.А., Колесникова Л.И., Колесников С.И. Окислительный стресс: патогенетическая роль в развитии сахарного диабета и его осложнения, терапевтические подходы к коррекции // Бюллетень экспериментальной биологии и медицины. 2021. Т. 171, № 2. С. 136–149. DOI: 10.1007/s10517-021-05191-7

[21] Bigagli E, Lodovici M. Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications. Oxid Med Cell Longev. 2019;2019:5953685. DOI: 10.1155/2019/5953685

[22] Bigagli E., Lodovici M. Circulating Oxidative Stress Biomarkers in Clinical Studies on Type 2 Diabetes and Its Complications // Oxid Med Cell Longev. 2019. Vol. 2019. ID5953685. DOI: 10.1155/2019/5953685

[23] Durnev AD. Modifikatsiya mutatsionnogo protsessa v kletkakh cheloveka. Annals of the Russian academy of medical sciences. 2001;(10):70–76. (In Russ.)

[24] Дурнев А.Д. Модификация мутационного процесса в клетках человека // Вестник РАМН. 2001. № 10. С. 70–76.

[25] Anatomo-Terapevticheski-Khimicheskaya (ATKH) sistema klassifikatsii [Internet]. [cited 2021 May 15]. Available from: https://www.vidal.ru/drugs/atc (In Russ.)

[26] Анатомо-Терапевтически-Химическая (АТХ) система классификации [Internet]. Дата обращения: 15.05.2021. Доступ по ссылке: https://www.vidal.ru/drugs/atc

[27] Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Dedov II, Shestakova MV, Mayorov AYu, eds. 9th edition. Diabetes mellitus. 2019;22(1S1):1–144. (In Russ.) DOI: org/10.14341/DM221S1

[28] Дедов И.И., Шестакова М.В., Майоров А.Ю., и др. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. 9-й выпуск. Под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова // Сахарный диабет. 2019. Т. 22, № 1S1. С. 1–144. DOI: 10.14341/DM221S1

[29] Othman EM, Leyh A, Stopper H. Insulin mediated DNA damage in mammalian colon cells and human lymphocytes in vitro. Mutat Res. 2013;745-746:34-9. DOI: 10.1016/j.mrfmmm.2013.03.006

[30] Othman E.M., Leyh A., Stopper H. Insulin mediated DNA damage in mammalian colon cells and human lymphocytes in vitro // Mutat Res. 2013. Vol. 745–746. P. 34–39. DOI: 10.1016/j.mrfmmm.2013.03.006

[31] Othman EM, Oli RG, Arias-Loza PA, et al. Metformin Protects Kidney Cells From Insulin-Mediated Genotoxicity In Vitro and in Male Zucker Diabetic Fatty Rats. Endocrinology. 2016;157(2):548–559. DOI: 10.1210/en.2015-1572

[32] Othman E.M., Oli R.G., Arias-Loza P.A., et al. Metformin Protects Kidney Cells From Insulin-Mediated Genotoxicity In Vitro and in Male Zucker Diabetic Fatty Rats // Endocrinology. 2016. Vol. 157. No. 2. P. 548–559. DOI: 10.1210/en.2015-1572

[33] Tokajuk A, Krzyżanowska-Grycel E, Tokajuk A, et al. Antidiabetic drugs and risk of cancer. Pharmacol Rep. 2015;67(6):1240–1250. DOI: 10.1016/j.pharep.2015.05.005

[34] Tokajuk A., Krzyżanowska-Grycel E., Tokajuk A., et al. Antidiabetic drugs and risk of cancer // Pharmacol Rep. 2015. Vol. 67. No. 6. P. 1240–1250. DOI: 10.1016/j.pharep.2015.05.005

[35] Othman EM, Altabaa T, Hintzsche H, Stopper H. IR and IGF-1R expression affects insulin induced proliferation and DNA damage. Toxicol In Vitro. 2017;39:68–74. DOI: 10.1016/J.TIV.2016.11.011

[36] Othman E.M., Altabaa T., Hintzsche H., Stopper H. IR and IGF-1R expression affects insulin induced proliferation and DNA damage // Toxicol In Vitro. 2017. Vol. 39. P. 68–74. DOI: 10.1016/j.tiv.2016.11.011

[37] HUMALOG® Product Monograph [Internet]. [cited 2021 May 15] Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjclZyw_KPvAhVGxIsKHZvlBE4QFjAOegQIBBAD&url=https%3A%2F%2Fpdf.hres.ca%2Fdpd_pm%2F00003299.PDF&usg=AOvVaw3qP_2gNpNQ3fN1X-CspEXC

[38] HUMALOG® Product Monograph [Internet]. Дата обращения: 15.05.2021. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwjclZyw_KPvAhVGxIsKHZvlBE4QFjAOegQIBBAD&url=https%3A%2F%2Fpdf.hres.ca%2Fdpd_pm%2F00003299.PDF&usg=AOvVaw3qP_2gNpNQ3fN1X-CspEXC

[39] Center for drug evaluation and research. Insulin Aspart [rDNA Origin] Injection [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiEvp7egaTvAhVD_SoKHTjvCvkQFjACegQIBRAD&url=https%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2013 %2F020986Orig1s061.pdf&usg=AOvVaw3DAicbE-EHyrHrRmiEjIU6

[40] Center for drug evaluation and research. Insulin Aspart [rDNA Origin] Injection [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiEvp7egaTvAhVD_SoKHTjvCvkQFjACegQIBRAD&url=https%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2013 %2F020986Orig1s061.pdf&usg=AOvVaw3DAicbE-EHyrHrRmiEjIU6

[41] NovoRapid Approval Scientific discussion [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiEvp7egaTvAhVD_SoKHTjvCvkQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fscientific-discussion%2Fnovorapid-epar-scientific-discussion_en.pdf&usg=AOvVaw38mmTxmMGBpGUYcoSzhqTD

[42] NovoRapid Approval Scientific discussion [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiEvp7egaTvAhVD_SoKHTjvCvkQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fscientific-discussion%2Fnovorapid-epar-scientific-discussion_en.pdf&usg=AOvVaw38mmTxmMGBpGUYcoSzhqTD

[43] Apidra Approval Scientific discussion [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiNzp6Ig6TvAhVC2SoKHRI8BzkQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Fapidra-epar-scientific-discussion_en.pdf&usg=AOvVaw3viOO4MIxkPFOeYV0rt8Pc

[44] Apidra Approval Scientific discussion [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiNzp6Ig6TvAhVC2SoKHRI8BzkQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Fapidra-epar-scientific-discussion_en.pdf&usg=AOvVaw3viOO4MIxkPFOeYV0rt8Pc

[45] Center for drug evaluation and research. Application number 21–629. Pharmacology review [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiNzp6Ig6TvAhVC2SoKHRI8BzkQFjABegQIFhAD&url=https%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2004 %2F21-629_Apidra_Pharmr_P1.pdf&usg=AOvVaw0Xh-xiYWgUJMk6jWLchV2g

[46] Center for drug evaluation and research. Application number 21–629. Pharmacology review [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiNzp6Ig6TvAhVC2SoKHRI8BzkQFjABegQIFhAD&url=https%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2004 %2F21-629_Apidra_Pharmr_P1.pdf&usg=AOvVaw0Xh-xiYWgUJMk6jWLchV2g

[47] Center for drug evaluation and research. Application number 21–536. Pharmacology review(s) [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwisgKqVhaTvAhUhlosKHeJDDgwQFjACegQIExAD&url=http%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2005 %2F021-536_Levemir_pharmr.pdf&usg=AOvVaw3rpOhO3TifQYrMyRFaC_xy

[48] Center for drug evaluation and research. Application number 21–536. Pharmacology review(s) [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwisgKqVhaTvAhUhlosKHeJDDgwQFjACegQIExAD&url=http%3A%2F%2Fwww.accessdata.fda.gov%2Fdrugsatfda_docs%2Fnda%2F2005 %2F021-536_Levemir_pharmr.pdf&usg=AOvVaw3rpOhO3TifQYrMyRFaC_xy

[49] Flevemir Approval Scientific discussion [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwisgKqVhaTvAhUhlosKHeJDDgwQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Flevemir-epar-scientific-discussion_en.pdf&usg=AOvVaw2TiEsZCAKiZRdTFlfmzrdo

[50] Flevemir Approval Scientific discussion [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwisgKqVhaTvAhUhlosKHeJDDgwQFjAAegQIARAD&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Flevemir-epar-scientific-discussion_en.pdf&usg=AOvVaw2TiEsZCAKiZRdTFlfmzrdo

[51] Mironov AN. Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast’. 1. Moscow: Grif i K, 2012. 944 p. (In Russ.)

[52] Руководство по проведению доклинических исследований лекарственных средств Ч. 1. Под ред. А.Н. Миронова. М.: Гриф и К, 2012. 944 с.

[53] Renner HW, Münzner R. Mutagenicity of sulphonylureas. Mutat Res. 1980;77(4):349–355. DOI: 10.1016/0165-1218(80)90007-5

[54] Renner H.W., Münzner R. Mutagenicity of sulphonylureas // Mutat Res. 1980. Vol. 77. No. 4. P. 349–355. DOI: 10.1016/0165-1218(80)90007-5

[55] Kar RN, Mukherjee B, Mukherjee SK. Mutagenic evaluation of tolbutamide and glybenclamide on the bone marrow cells of mice. Toxicol Lett. 1986;34(2–3):153–157. DOI: 10.1016/0378-4274(86)90205-5

[56] Kar R.N., Mukherjee B., Mukherjee S.K. Mutagenic evaluation of tolbutamide and glybenclamide on the bone marrow cells of mice // Toxicol Lett. 1986. Vol. 34. No. 2–3. P. 153–157. DOI: 10.1016/0378-4274(86)90205-5

[57] Sekena H, El-Aziem A, Hassan MA. Genetic and Ultrastructural studies in bone marrow and testis of mice cells under the effect of Glurenor drug. The Egyptian Journal of Hospital Medicine. 2003;12(1):62–71. DOI: 10.21608/ejhm.2003.18246

[58] Sekena H., El-Aziem A., Hassan M.A. Genetic and Ultrastructural studies in bone marrow and testis of mice cells under the effect of Glurenor drug // The Egyptian Journal of Hospital Medicine. 2003. Vol. 12. No. 1. P. 62–71. DOI: 10.21608/ejhm.2003.18246

[59] Bedir A, Aliyazicioglu Y, Bilgici B, et al. Assessment of genotoxicity in rats treated with the antidiabetic agent, pioglitazone. Environ Mol Mutagen. 2008;49(3):185–191. DOI: 10.1002/em.20365

[60] Bedir A., Aliyazicioglu Y., Bilgici B., et al. Assessment of genotoxicity in rats treated with the antidiabetic agent, pioglitazone // Environ Mol Mutagen. 2008. Vol. 49. No. 3. P. 185–191. DOI: 10.1002/em.20365

[61] Alzoubi K, Khabour O, Hussain N, et al. Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone. Mutat Res. 2012;748(1–2):48–51. DOI: 10.1016/j.mrgentox.2012.06.009

[62] Alzoubi K., Khabour O., Hussain N., et al. Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone // Mutat Res. 2012. Vol. 748. No. 1–2. P. 48–51. DOI: 10.1016/j.mrgentox.2012.06.009

[63] Bedir A, Aliyazicioglu Y, Kahraman H, et al. Genotoxicity in rats treated with the antidiabetic agent, rosiglitazone. Environ Mol Mutagen. 2006;47(9):718–724. DOI: 10.1002/em.20261

[64] Bedir A., Aliyazicioglu Y., Kahraman H., et al. Genotoxicity in rats treated with the antidiabetic agent, rosiglitazone // Environ Mol Mutagen. 2006. Vol. 47. No. 9. P. 718–724. DOI: 10.1002/em.20261

[65] Yuzbasioglu D, Enguzel-Alperen C, Unal F. Investigation of in vitro genotoxic effects of an anti-diabetic drug sitagliptin. Food Chem Toxicol. 2018;112:235–241. DOI: 10.1016/j.fct.2018.01.003

[66] Yuzbasioglu D., Enguzel-Alperen C., Unal F. Investigation of in vitro genotoxic effects of an anti-diabetic drug sitagliptin // Food Chem Toxicol. 2018. Vol. 112. P. 235–241. DOI: 10.1016/j.fct.2018.01.003

[67] Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658–664. DOI: 10.12659/MSMBR.889344

[68] Nasri H., Rafieian-Kopaei M. Metformin: Current knowledge // J Res Med Sci. 2014. Vol. 19. No. 7. P. 658–664. DOI: 10.12659/MSMBR.889344

[69] Kalashnikova MF, Belousov DY, Suntsov YI, et al. Pharmacoepidemiological and pharmacoeconomic analyses of the utilization of hypoglycaemic drugs in patients with type 2 diabetes mellitus in Moscow. Diabetes mellitus. 2015;18(2):32–46. (In Russ.) DOI: 10.14341/DM2015232-46

[70] Калашникова М.Ф., Белоусов Д.Ю., Сунцов Ю.И., и др. Фармакоэпидемиологический анализ потребления сахароснижающих лекарственных средств у больных сахарным диабетом 2 типа в городе Москве // Сахарный диабет. 2015. Т. 18, № 2. С. 32–46. DOI: 10.14341/DM2015232-46

[71] Marshall SM. 60 years of metformin use: a glance at the past and a look to the future. Diabetologia. 2017;60(9):1561–1565. DOI: 10.1007/s00125-017-4343-y

[72] Marshall S.M. 60 years of metformin use: a glance at the past and a look to the future // Diabetologia. 2017. Vol. 60. No. 9. P. 1561–1565. DOI: 10.1007/s00125-017-4343-y

[73] Attia SM, Helal GK, Alhaider AA. Assessment of genomic instability in normal and diabetic rats treated with metformin. Chem Biol Interact. 2009;180(2):296–304. DOI: 10.1016/j.cbi.2009.03.001

[74] Attia S.M., Helal G.K., Alhaider A.A. Assessment of genomic instability in normal and diabetic rats treated with metformin // Chem Biol Interact. 2009. Vol. 180. No. 2. P. 296–304. DOI: 10.1016/j.cbi.2009.03.001

[75] Amador RR, Longo JP, Lacava ZG, et al. Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells. Genet Mol Biol. 2012;35(1):153–158. DOI: 10.1590/s1415-47572011005000060

[76] Amador R.R., Longo J.P., Lacava Z.G., et al. Metformin (dimethyl-biguanide) induced DNA damage in mammalian cells // Genet Mol Biol. 2012. Vol. 35. No. 1. P. 153–158. DOI: 10.1590/s1415-47572011005000060

[77] Malek HA, Hassanin A, Aziz HA, Dahtory FE. In vitro assessment of the mutagenic effect of Metformin. J Chem Pharm Res. 2015;7(6):879–886.

[78] Malek H.A., Hassanin A., Aziz H.A., Dahtory F.E. In vitro assessment of the mutagenic effect of Metformin // J Chem Pharm Res. 2015. Vol. 7. No. 6. P. 879–886.

[79] Sant’Anna JR, Yajima JP, Rosada LJ, et al. Metformin’s performance in in vitro and in vivo genetic toxicology studies. Exp Biol Med (Maywood). 2013;238(7):803–810. DOI: 10.1177/1535370213480744

[80] Sant’Anna J.R., Yajima J.P., Rosada L.J., et al. Metformin’s performance in in vitro and in vivo genetic toxicology studies // Exp Biol Med (Maywood). 2013. Vol. 238. No. 7. P. 803–810. DOI: 10.1177/1535370213480744

[81] Rabbani SI, Devi K, Khanam S. Role of Pioglitazone with Metformin or Glimepiride on Oxidative Stress-induced Nuclear Damage and Reproductive Toxicity in Diabetic Rats. Malays J Med Sci. 2010;17(1):3–11.

[82] Rabbani S.I., Devi K., Khanam S. Role of Pioglitazone with Metformin or Glimepiride on Oxidative Stress-induced Nuclear Damage and Reproductive Toxicity in Diabetic Rats // Malays J Med Sci. 2010. Vol. 17. No. 1. P. 3–11

[83] OECD. Test No. 489: In Vivo Mammalian Alkaline Comet Assay. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. 2016. https://doi.org/10.1787/9789264264885-en

[84] OECD. Test No. 489: In Vivo Mammalian Alkaline Comet Assay. OECD Guidelines for the Testing of Chemicals, Section 4. OECD Publishing, Paris. 2016. DOI: 10.1787/9789264264885-en.

[85] Najafi M, Cheki M, Rezapoor S, et al. Metformin: Prevention of genomic instability and cancer: A review. Mutat Res Genet Toxicol Environ Mutagen. 2018;827:1–8. DOI: 10.1016/j.mrgentox.2018.01.007

[86] Najafi M., Cheki M., Rezapoor S., et al. Metformin: Prevention of genomic instability and cancer: A review // Mutat Res Genet Toxicol Environ Mutagen. 2018. Vol. 827. P. 1–8. DOI: 10.1016/j.mrgentox.2018.01.007

[87] Aleisa AM, Al-Rejaie SS, Bakheet SA, et al. Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice. Mutat Res. 2007;634(1–2):93–100. DOI: 10.1016/j.mrgentox.2007.06.005

[88] Aleisa A.M., Al-Rejaie S.S., Bakheet S.A., et al. Effect of metformin on clastogenic and biochemical changes induced by adriamycin in Swiss albino mice // Mutat Res. 2007. Vol. 634. No. 1–2. P. 93–100. DOI: 10.1016/j.mrgentox.2007.06.005

[89] Cheki M, Shirazi A, Mahmoudzadeh A, et al. The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes. Mutat Res. 2016;809:24–32. DOI: 10.1016/j.mrgentox.2016.09.001

[90] Cheki M., Shirazi A., Mahmoudzadeh A., et al. The radioprotective effect of metformin against cytotoxicity and genotoxicity induced by ionizing radiation in cultured human blood lymphocytes // Mutat Res. 2016. Vol. 809. P. 24–32. DOI: 10.1016/j.mrgentox.2016.09.001

[91] Kanigür-Sultuybek G, Ozdas SB, Curgunlu A, et al. Does metformin prevent short-term oxidant-induced dna damage? In vitro study on lymphocytes from aged subjects. J Basic Clin Physiol Pharmacol. 2007;18(2):129–140. DOI: 10.1515/jbcpp.2007.18.2.129

[92] Kanigür-Sultuybek G., Ozdas S.B., Curgunlu A., et al. Does metformin prevent short-term oxidant-induced dna damage? In vitro study on lymphocytes from aged subjects // J Basic Clin Physiol Pharmacol. 2007. Vol. 18. No. 2. P. 129–140. DOI: 10.1515/jbcpp.2007.18.2.129

[93] Roshdy HM, Kassem SM. Genetic effects of Januvia and Galvus alone or with metformin on pregnant female mice and their embryos. World Applied Sciences Journal. 2013;25:1690–1698. DOI: 10.5829/idosi.wasj.2013.25.12.76142

[94] Roshdy H.M., Kassem S.M. Genetic effects of Januvia and Galvus alone or with metformin on pregnant female mice and their embryos // World Appl Sci J. 2013. Vol. 25. P. 1690–1698. DOI: 10.5829/idosi.wasj.2013.25.12.76142

[95] Esteghamati A, Eskandari D, Mirmiranpour H, et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial. Clin Nutr. 2013;32(2):179–185. DOI: 10.1016/j.clnu.2012.08.006

[96] Esteghamati A., Eskandari D., Mirmiranpour H., et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: a randomized clinical trial // Clin Nutr. 2013. Vol. 32. No. 2. P. 179–185. DOI: 10.1016/j.clnu.2012.08.006

[97] Dogan Turacli I, Candar T, Yuksel EB, et al. Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes. Biochimie. 2018;154:62–68. DOI: 10.1016/j.biochi.2018.08.002

[98] Dogan Turacli I., Candar T., Yuksel E.B., et al. Potential effects of metformin in DNA BER system based on oxidative status in type 2 diabetes // Biochimie. 2018. Vol. 154. P. 62–68. DOI: 10.1016/j.biochi.2018.08.002

[99] Safe S, Nair V, Karki K. Metformin-induced anticancer activities: recent insights. Biol Chem. 2018;399(4):321–335. DOI: 10.1515/hsz-2017-0271

[100] Safe S., Nair V., Karki K. Metformin-induced anticancer activities: recent insights // Biol Chem. 2018. Vol. 399. No. 4. P. 321–335. DOI: 10.1515/hsz-2017-0271

[101] Anisimov VN. Do metformin a real anticarcinogen? A critical reappraisal of experimental data. Ann Transl Med. 2014;2(6):60. DOI: 10.3978/j.issn.2305-5839.2014.06.02

[102] Anisimov VN. Do metformin a real anticarcinogen? A critical reappraisal of experimental data. Ann Transl Med . Vol. 2. No. 6. P. 60. DOI: 10.3978/j.issn.2305-5839.2014.06.02

[103] Noto H, Goto A, Tsujimoto T, Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis. PLoS One. 2012;7(3): e33411. DOI: 10.1371/journal.pone.0033411

[104] Noto H., Goto A., Tsujimoto T., Noda M. Cancer risk in diabetic patients treated with metformin: a systematic review and meta-analysis // PLoS One. 2012. Vol. 7. No. 3. ID e33411. DOI: 10.1371/journal.pone.0033411

[105] Zaidi S, Gandhi J, Joshi G, et al. The anticancer potential of metformin on prostate cancer. Prostate Cancer Prostatic Dis. 2019;22(3):351–361. DOI: 10.1038/s41391-018-0085-2

[106] Zaidi S., Gandhi J., Joshi G., et al. The anticancer potential of metformin on prostate cancer // Prostate Cancer Prostatic Dis. 2019. Vol. 22. No. 3. P. 351–361. DOI: 10.1038/s41391-018-0085-2

[107] Tang GH, Satkunam M, Pond GR, et al. Association of Metformin with Breast Cancer Incidence and Mortality in Patients with Type II Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis. Cancer Epidemiol Biomarkers Prev. 2018;27(6):627–635. DOI: 10.1158/1055-9965.EPI-17-0936

[108] Tang G.H., Satkunam M., Pond G.R., et al. Association of Metformin with Breast Cancer Incidence and Mortality in Patients with Type II Diabetes: A GRADE-Assessed Systematic Review and Meta-analysis // Cancer Epidemiol Biomarkers Prev. 2018. Vol. 27. No. 6. P. 627–635. DOI: 10.1158/1055-9965.EPI-17-0936

[109] Yao L, Liu M, Huang Y, et al. Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis. Dis Markers. 2019;2019:6230162. DOI: 10.1155/2019/6230162

[110] Yao L., Liu M., Huang Y., et al. Metformin Use and Lung Cancer Risk in Diabetic Patients: A Systematic Review and Meta-Analysis // Dis Markers. 2019. Vol. 2019. ID6230162. DOI: 10.1155/2019/6230162

[111] Heckman-Stoddard BM, DeCensi A, Sahasrabuddhe VV, Ford LG. Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia. 2017;60(9):1639–1647. DOI: 10.1007/s00125-017-4372-6

[112] Heckman-Stoddard B.M., DeCensi A., Sahasrabuddhe V.V., Ford L.G. Repurposing metformin for the prevention of cancer and cancer recurrence // Diabetologia. 2017. Vol. 60. No. 9. P. 1639–1647. DOI: 10.1007/s00125-017-4372-6

[113] Podhorecka M, Ibanez B, Dmoszyńska A. Metformin – its potential anti-cancer and anti-aging effects. Postepy Hig Med Dosw (Online). 2017;71:170–175. DOI: 10.5604/01.3001.0010.3801

[114] Podhorecka M., Ibanez B., Dmoszyńska A. Metformin – its potential anti-cancer and anti-aging effects // Postepy Hig Med Dosw (Online). 2017. Vol. 71. P. 170–175. DOI: 10.5604/01.3001.0010.3801

[115] Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia. 2017;60(9):1577–1585. DOI: 10.1007/s00125-017-4342-z

[116] Rena G., Hardie D.G., Pearson E.R. The mechanisms of action of metformin // Diabetologia. 2017. Vol. 60. No. 9. P. 1577–1585. DOI: 10.1007/s00125-017-4342-z

[117] Tseng CH. Thyroid cancer risk is not increased in diabetic patients. PLoS One. 2012;7(12): e53096. DOI: 10.1371/journal.pone.0053096

[118] Tseng C.H. Thyroid cancer risk is not increased in diabetic patients // PLoS One. 2012. Vol. 7. No. 12. ID e53096. DOI: 10.1371/journal.pone.0053096

[119] de Sant’Anna JR, Franco CC, Mathias PC, de Castro-Prado MA. Assessment of in vivo and in vitro genotoxicity of glibenclamide in eukaryotic cells. PLoS One. 2015;10(3): e0120675. DOI: 10.1371/journal.pone.0120675

[120] de Sant’Anna JR, Franco CC, Mathias PC, de Castro-Prado MA. Assessment of in vivo and in vitro genotoxicity of glibenclamide in eukaryotic cells. PLoS One. 2015. Vol. 10. No. 3. ID: e0120675. DOI: 10.1371/journal.pone.0120675

[121] Sarkar A, Tiwari A, Bhasin PS, Mitra M. Pharmacological and Pharmaceutical Profile of Gliclazide: A Review. J Appl Pharm Sci. 2011;1(9):11–19.

[122] Sarkar A., Tiwari A., Bhasin P.S., Mitra M. Pharmacological and Pharmaceutical Profile of Gliclazide: A Review // J Appl Pharm Sci. 2011. Vol. 1. No. 9. P. 11–19.

[123] Pouri M, Shaghaghi Z, Ghasemi A, Hosseinimehr SJ. Radioprotective Effect of Gliclazide as an Anti-Hyperglycemic Agent Against Genotoxicity Induced by Ionizing Radiation on Human Lymphocytes. Cardiovasc Hematol Agents Med Chem. 2019;17(1):40–46. DOI: 10.2174/1871525717666190524092918

[124] Pouri M., Shaghaghi Z., Ghasemi A., Hosseinimehr S.J. Radioprotective Effect of Gliclazide as an Anti-Hyperglycemic Agent Against Genotoxicity Induced by Ionizing Radiation on Human Lymphocytes // Cardiovasc Hematol Agents Med Chem. 2019. Vol. 17. No. 1. P. 40–46. DOI: 10.2174/1871525717666190524092918

[125] Rabbani SI, Devi K, Khanam S. Inhibitory effect of glimepiride on nicotinamide-streptozotocin induced nuclear damages and sperm abnormality in diabetic Wistar rats. Indian J Exp Biol. 2009;47(10):804–810.

[126] Rabbani S.I., Devi K., Khanam S. Inhibitory effect of glimepiride on nicotinamide-streptozotocin induced nuclear damages and sperm abnormality in diabetic Wistar rats // Indian J Exp Biol. 2009. Vol. 47. No. 10. P. 804–810.

[127] Brambilla G, Martelli A. Update on genotoxicity and carcinogenicity testing of 472 marketed pharmaceuticals. Mutat Res. 2009;681(2–3):209–229. DOI: 10.1016/j.mrrev.2008.09.002

[128] Brambilla G., Martelli A. Update on genotoxicity and carcinogenicity testing of 472 marketed pharmaceuticals // Mutat Res. 2009. Vol. 681. No. 2–3. P. 209–229. DOI: 10.1016/j.mrrev.2008.09.002

[129] Smith MT. Mechanisms of troglitazone hepatotoxicity. Chem Res Toxicol. 2003;16(6):679–687. DOI: 10.1021/tx034033e

[130] Smith M.T. Mechanisms of troglitazone hepatotoxicity // Chem Res Toxicol. 2003. Vol. 16. No. 6. P. 679–687. DOI: 10.1021/tx034033e

[131] Nathan DM. Rosiglitazone and cardiotoxicity — weighing the evidence. N Engl J Med. 2007;357(1):64–66. DOI: 10.1056/NEJMe078117

[132] Nathan D.M. Rosiglitazone and cardiotoxicity – weighing the evidence // N Engl J Med. 2007. Vol. 357. No. 1. P. 64–66. DOI: 10.1056/NEJMe078117

[133] Amein KA, Hamdy MM, Abd El-Emam RA, Osman FH. The effect of pioglitagone on genomic instability in induced diabetic rats. Research Journal of Applied Biotechnology. 2016; Special volume for the first International Conference of Genetic Engineering and Biotechnology:68–80. DOI: 10.21608/rjab.2016.59636

[134] Amein K.A., Hamdy M.M., Abd El-Emam R.A., Osman F.H. The effect of pioglitagone on genomic instability in induced diabetic rats // Research Journal of Applied Biotechnology. 2016. Special volume for the first International Conference of Genetic Engineering and Biotechnology. P. 68–80. DOI: 10.21608/rjab.2016.59636

[135] Morais JF, Sant’Anna JR, Pereira TS, et al. Genotoxic investigation of a thiazolidinedione PPARγ agonist using the in vitro micronucleus test and the in vivo homozygotization assay. Mutagenesis. 2016;31(4):417–424. DOI: 10.1093/mutage/gew003

[136] Morais J.F., Sant’Anna J.R., Pereira T.S., et al. Genotoxic investigation of a thiazolidinedione PPARγ agonist using the in vitro micronucleus test and the in vivo homozygotization assay // Mutagenesis. 2016. Vol. 31. No. 4. P. 417–424. DOI: 10.1093/mutage/gew003

[137] Drab SR. Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy. Curr Diabetes Rev. 2016;12(4):403–413. DOI: 10.2174/1573399812666151223093841

[138] Drab S.R. Glucagon-Like Peptide-1 Receptor Agonists for Type 2 Diabetes: A Clinical Update of Safety and Efficacy // Curr Diabetes Rev. 2016. Vol. 12. No. 4. P. 403–413. DOI: 10.2174/1573399812666151223093841

[139] Guo X, Yang Q, Dong J, et al. Tumour Risk with Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus Patients: A Systematic Review. Clin Drug Investig. 2016;36(6):433–441. DOI: 10.1007/s40261-016-0389-8

[140] Guo X., Yang Q., Dong J., et al. Tumour Risk with Once-Weekly Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus Patients: A Systematic Review // Clin Drug Investig. 2016. Vol. 36. No. 6. P. 433–441. DOI: 10.1007/s40261-016-0389-8

[141] Alves C, Batel-Marques F, Macedo AF. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer. Diabetes Res Clin Pract. 2012;98(2):271–284. DOI: 10.1016/j.diabres.2012.09.008

[142] Alves C., Batel-Marques F., Macedo A.F. A meta-analysis of serious adverse events reported with exenatide and liraglutide: acute pancreatitis and cancer // Diabetes Res Clin Pract. 2012. Vol. 98. No. 2. P. 271–284. DOI: 10.1016/j.diabres.2012.09.008

[143] Azqueta A, Slyskova J, Langie SA, et al. Comet assay to measure DNA repair: approach and applications. Front Genet. 2014;5:288. DOI: 10.3389/fgene.2014.00288

[144] Azqueta A., Slyskova J., Langie S.A., et al. Comet assay to measure DNA repair: approach and applications // Front Genet. 2014. Vol. 5. P. 288. DOI: 10.3389/fgene.2014.00288

[145] Byetta Approval Scientific discussion [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=2ahUKEwiK1frvgcPpAhVBAhAIHeXBDMkQFjABegQIAxAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Fbyetta-epar-scientific-discussion_en.pdf&usg=AOvVaw2BukkG_ld6RLWhosmSMDe-

[146] Byetta Approval Scientific discussion [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&cad=rja&uact=8&ved=2ahUKEwiK1frvgcPpAhVBAhAIHeXBDMkQFjABegQIAxAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fscientific-discussion%2Fbyetta-epar-scientific-discussion_en.pdf&usg=AOvVaw2BukkG_ld6RLWhosmSMDe-

[147] Assessment report for Victoza [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji-86flqzrAhUBAxAIHWEwCaYQFjAAegQIBBAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fema-redirect%3Fredirect_type%3Djsp%26webContentId%3DWC500050016&usg=AOvVaw3d6IbqsAoquGGnt9M_yV4_

[148] Assessment report for Victoza [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwji-86flqzrAhUBAxAIHWEwCaYQFjAAegQIBBAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fema-redirect%3Fredirect_type%3Djsp%26webContentId%3DWC500050016&usg=AOvVaw3d6IbqsAoquGGnt9M_yV4_

[149] Assessment report Lyxumia [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwitsaygl6zrAhWjxIsKHdq-DI8QFjAAegQIBBAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Flyxumia-epar-public-assessment-report_en.pdf&usg=AOvVaw35wDuXxjyiD-0fL2paBAZv

[150] Assessment report Lyxumia [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwitsaygl6zrAhWjxIsKHdq-DI8QFjAAegQIBBAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Flyxumia-epar-public-assessment-report_en.pdf&usg=AOvVaw35wDuXxjyiD-0fL2paBAZv

[151] Assessment report Ozempic [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjImuuUmKzrAhVp-yoKHTU9Bg4QFjAKegQIARAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Fozempic-epar-public-assessment-report_en.pdf&usg=AOvVaw1zFwSfvLP0ycmHePzsnI2u

[152] Assessment report Ozempic [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjImuuUmKzrAhVp-yoKHTU9Bg4QFjAKegQIARAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Fozempic-epar-public-assessment-report_en.pdf&usg=AOvVaw1zFwSfvLP0ycmHePzsnI2u

[153] Börçek Kasurka C, Elbistan M, Atmaca A, Atlı Şekeroğlu Z. In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin. Cytotechnology. 2019;71(6):1063–1077. DOI: 10.1007/s10616-019-00345-y

[154] Börçek Kasurka C., Elbistan M., Atmaca A., Atlı Şekeroğlu Z. In vitro cytogenetic assessment and comparison of vildagliptin and sitagliptin // Cytotechnology. 2019. Vol. 71. No. 6. P. 1063–1077. DOI: 10.1007/s10616-019-00345-y

[155] Annex I. Onglyza 2.5 and 5 mg film-coated tablets. Summary of product characteristics [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwi0iLvBgoPzAhWPnYsKHb80CV4QFnoECAIQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Fonglyza-epar-product-information_en.pdf&usg=AOvVaw1JdORt5TzuaemMnLSTnSOP

[156] Annex I. Onglyza 2.5 and 5 mg film-coated tablets. Summary of product characteristics [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwi0iLvBgoPzAhWPnYsKHb80CV4QFnoECAIQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Fonglyza-epar-product-information_en.pdf&usg=AOvVaw1JdORt5TzuaemMnLSTnSOP

[157] Bristol-Myers Squibb Company. ONGLYZA™ (saxagliptin) tablets. US prescribing information. 2011.

[158] Annex I. Vipidia 6.25, 12.5 and 25 mg film-coated tablets. Summary of product characteristics [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjk377SgoPzAhXrsIsKHWpWCK8QFnoECAIQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Fvipidia-epar-product-information_en.pdf&usg=AOvVaw2lKgOuaut8a473M-MAQeL8

[159] Annex I. Vipidia 6.25, 12.5 and 25 mg film-coated tablets. Summary of product characteristics [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjk377SgoPzAhXrsIsKHWpWCK8QFnoECAIQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Fvipidia-epar-product-information_en.pdf&usg=AOvVaw2lKgOuaut8a473M-MAQeL8

[160] Çadirci K, Türkez H, Özdemir Ö. The in vitro cytotoxicity, genotoxicity and oxidative damage potential of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, on cultured human mononuclear blood cells. Acta Endocrinol (Buchar). 2019;5(1):9–15. DOI: 10.4183/aeb.2019.9

[161] Çadirci K., Türkez H., Özdemir Ö. The in vitro cytotoxicity, genotoxicity and oxidative damage potential of the oral dipeptidyl peptidase-4 inhibitor, linagliptin, on cultured human mononuclear blood cells // Acta Endocrinol (Buchar). 2019. Vol. 5. No. 1. P. 9–15. DOI: 10.4183/aeb.2019.9

[162] Oz Gul O, Cinkilic N, Gul CB, et al. Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study. Mutat Res. 2013;757(1):31–35. DOI: 10.1016/j.mrgentox.2013.04.024

[163] Oz Gul O., Cinkilic N., Gul C.B., et al. Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study // Mutat Res. 2013. Vol. 757. No. 1. P. 31–35. DOI: 10.1016/j.mrgentox.2013.04.024

[164] Reilly TP, Graziano MJ, Janovitz EB, et al. Carcinogenicity risk assessment supports the chronic safety of dapagliflozin, an inhibitor of sodium-glucose co-transporter 2, in the treatment of type 2 diabetes mellitus. Diabetes Ther. 2014;5(1):73–96. DOI: 10.1007/s13300-014-0053-3

[165] Reilly T.P., Graziano M.J., Janovitz E.B., et al. Carcinogenicity risk assessment supports the chronic safety of dapagliflozin, an inhibitor of sodium-glucose co-transporter 2, in the treatment of type 2 diabetes mellitus // Diabetes Ther. 2014. Vol. 5. No. 1. P. 73–96. DOI: 10.1007/s13300-014-0053-3

[166] Bogdanffy MS, Stachlewitz RF, van Tongeren S, et al. Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin. Int J Toxicol. 2014;33(6):436–449. DOI: 10.1177/1091581814551648

[167] Bogdanffy M.S., Stachlewitz R.F., van Tongeren S., et al. Nonclinical safety of the sodium-glucose cotransporter 2 inhibitor empagliflozin // Int J Toxicol. 2014. Vol. 33. No. 6. P. 436–449. DOI: 10.1177/1091581814551648

[168] Assessment report Canagliflozin [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiWj_bZpqzrAhVukIsKHcXYAngQFjABegQIARAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Finvokana-epar-public-assessment-report_en.pdf&usg=AOvVaw1VbOa--peFCGjDAZ8xdrcQ

[169] Assessment report Canagliflozin [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwiWj_bZpqzrAhVukIsKHcXYAngQFjABegQIARAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Finvokana-epar-public-assessment-report_en.pdf&usg=AOvVaw1VbOa--peFCGjDAZ8xdrcQ

[170] Smith JD, Huang Z, Escobar PA, et al. A Predominant Oxidative Renal Metabolite of Empagliflozin in Male Mice Is Cytotoxic in Mouse Renal Tubular Cells but not Genotoxic. Int J Toxicol. 2017;36(6):440–448. DOI: 10.1177/1091581817735090

[171] Smith J.D., Huang Z., Escobar P.A., et al. A Predominant Oxidative Renal Metabolite of Empagliflozin in Male Mice Is Cytotoxic in Mouse Renal Tubular Cells but not Genotoxic // Int J Toxicol. 2017. Vol. 36. No. 6. P. 440–448. DOI: 10.1177/1091581817735090

[172] Assessment report Steglatro [Internet]. Available from: https://www.ema.europa.eu/en/ema-redirect?redirect_type=document&lang=en&doc_id=WC500246920%20&doc_ext=pdf

[173] Assessment report Steglatro [Internet]. Доступ по ссылке: https://www.ema.europa.eu/en/ema-redirect?redirect_type=document&lang=en&doc_id=WC500246920%20&doc_ext=pdf

[174] Annex I. Repaglinide Accord 0.5 mg tablets. Summary of product characteristics [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjCs5vCpKzrAhXv-yoKHRkoA30QFjAKegQIAxAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Frepaglinide-accord-epar-product-information_en.pdf&usg=AOvVaw2KUEtCsjKl5piGAJuOkYMJ

[175] Annex I. Repaglinide Accord 0.5 mg tablets. Summary of product characteristics [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&cad=rja&uact=8&ved=2ahUKEwjCs5vCpKzrAhXv-yoKHRkoA30QFjAKegQIAxAB&url=https%3A%2F%2Fwww.ema.europa.eu%2Fen%2Fdocuments%2Fproduct-information%2Frepaglinide-accord-epar-product-information_en.pdf&usg=AOvVaw2KUEtCsjKl5piGAJuOkYMJ

[176] CHMP assessment report Bydureon [Internet]. Available from: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwig06WcgoPzAhXFlYsKHcq9CtUQFnoECBYQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Fbydureon-epar-public-assessment-report_en.pdf&usg=AOvVaw1OllVdjrn7ox25ZCCzJ_BZ

[177] CHMP assessment report Bydureon [Internet]. Доступ по ссылке: https://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=&ved=2ahUKEwig06WcgoPzAhXFlYsKHcq9CtUQFnoECBYQAQ&url=https%3A%2F%2Fwww.ema.europa.eu%2Fdocuments%2Fassessment-report%2Fbydureon-epar-public-assessment-report_en.pdf&usg=AOvVaw1OllVdjrn7ox25ZCCzJ_BZ

[178] European Medicines Agеncy. ICH S2 (R1) Genotoxicity testing and data interpretation for pharmaceuticals intended for human use — Step 5. 2013. Available from: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-s2-r1-genotoxicity-testing-data-interpretation-pharmaceuticals-intended-human-use-step_en.pdf

[179] European Medicines Agеncy. ICH S2 (R1) Genotoxicity testing and data interpretation for pharmaceuticals intended for human use — Step 5. 2012. Доступ по ссылке: https://www.ema.europa.eu/en/documents/scientific-guideline/ich-guideline-s2-r1-genotoxicity-testing-data-interpretation-pharmaceuticals-intended-human-use-step_en.pdf

[180] Durnev AD, Seredenin SB. Co-mutagenesis as new vistas in genotoxicology. Byulleten’ eksperimental’noj biologii i mediciny. 2003;135(6):604–612. (In Russ.) DOI: 10.1023/A:1025410612571

[181] Дурнев А.Д., Середенин С.Б. Комутагенез — новое направление исследований в генотоксикологии // Бюллетень экспериментальной биологии и медицины. 2003. Т. 135, № 6. С. 604–612. DOI: 10.1023/A:1025410612571

[182] Durnev AD, Daugel’-Dauge NO, Seredenin SB. Comutagen interaction of verapamil and ribavirin. Experimental and clinical pharmacology. 2006;69(1):56–59. (In Russ.)

[183] Дурнев А.Д., Даугель-Дауге Н.О., Середенин С.Б. Комутагенное взаимодействие верапамила и рибавирина // Экспериментальная и клиническая фармакология. 2006. Т. 69, № 1. С. 56–59.

[184] Durnev AD, Zhanataev AK, Voronina ES, et al. Modification of Chemical Mutagenesis. In: Genotoxicity: Evaluation, Testing and Prediction. Andor K., Molnar H., editors. NY: Nova Science Publishers, 2009. 157–187 p.

[185] Durnev A.D., Zhanataev A.K., Voronina E.S., et al. Modification of Chemical Mutagenesis. In: Genotoxicity: Evaluation, Testing and Prediction. Andor K., Molnar H., editors. NY: Nova Science Publishers, 2009. P. 157–187.

[186] Corrêa CR, Garcia JL. DNA Damage in Chronic Heart Failure: Consequences Beyond those in the Heart. Arq Bras Cardiol. 2020;114(2):243–244. DOI: 10.36660/abc.20190884

[187] Corrêa C.R., Garcia J.L. DNA Damage in Chronic Heart Failure: Consequences Beyond those in the Heart // Arq Bras Cardiol. 2020. Vol. 114. No. 2. P. 243–244. DOI: 10.36660/abc.20190884

[188] Cervelli T, Borghini A, Galli A, Andreassi MG. DNA damage and repair in atherosclerosis: current insights and future perspectives. Int J Mol Sci. 2012;13(12):16929–16944. DOI: 10.3390/ijms131216929

[189] Cervelli T., Borghini A., Galli A., Andreassi M.G. DNA damage and repair in atherosclerosis: current insights and future perspectives // Int J Mol Sci. 2012. Vol. 13. No. 12. P. 16929–16944. DOI: 10.3390/ijms131216929

[190] Mahmoudi M, Mercer J, Bennett M. DNA damage and repair in atherosclerosis. Cardiovasc Res. 2006;71(2):259–268. DOI: 10.1016/j.cardiores.2006.03.002

[191] Mahmoudi M., Mercer J., Bennett M. DNA damage and repair in atherosclerosis // Cardiovasc Res. 2006. Vol. 71. No. 2. P. 259–268. DOI: 10.1016/j.cardiores.2006.03.002

[192] Schupp N, Stopper H, Heidland A. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers. Oxid Med Cell Longev. 2016;2016:3592042. DOI: 10.1155/2016/3592042

[193] Schupp N., Stopper H., Heidland A. DNA Damage in Chronic Kidney Disease: Evaluation of Clinical Biomarkers // Oxid Med Cell Longev. 2016. Vol. 2016. ID3592042. DOI: 10.1155/2016/3592042

[194] Mishra M, Lillvis J, Seyoum B, Kowluru RA. Peripheral Blood Mitochondrial DNA Damage as a Potential Noninvasive Biomarker of Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2016;57(10):4035–4044. DOI: 10.1167/iovs.16-19073

[195] Mishra M., Lillvis J., Seyoum B., Kowluru R.A. Peripheral Blood Mitochondrial DNA Damage as a Potential Noninvasive Biomarker of Diabetic Retinopathy // Invest Ophthalmol Vis Sci. 2016. Vol. 57. No. 10. P. 4035–4044. DOI: 10.1167/iovs.16-19073

[196] Madsen-Bouterse SA, Mohammad G, Kanwar M, Kowluru RA. Role of mitochondrial DNA damage in the development of diabetic retinopathy, and the metabolic memory phenomenon associated with its progression. Antioxid Redox Signal. 2010;13(6):797–805. DOI: 10.1089/ars.2009.2932

[197] Madsen-Bouterse S.A., Mohammad G., Kanwar M., Kowluru R.A. Role of mitochondrial DNA damage in the development of diabetic retinopathy, and the metabolic memory phenomenon associated with its progression // Antioxid Redox Signal. 2010. Vol. 13. No. 6. P. 797–805. DOI: 10.1089/ars.2009.2932

[198] Singh P, Jain A, Kaur G. Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage. Mol Cell Biochem. 2004;260(1–2):153–159. DOI: 10.1023/b: mcbi.0000026067.08356.13

[199] Singh P., Jain A., Kaur G. Impact of hypoglycemia and diabetes on CNS: correlation of mitochondrial oxidative stress with DNA damage // Mol Cell Biochem. 2004. Vol. 260. No. 1–2. P. 153–159. DOI: 10.1023/b: mcbi.0000026067.08356.13

[200] Jackson AL, Loeb LA. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat Res. 2001;477(1–2):7–21. DOI: 10.1016/s0027-5107(01)00091-4

[201] Jackson A.L., Loeb L.A. The contribution of endogenous sources of DNA damage to the multiple mutations in cancer // Mutat Res. 2001. Vol. 477. No. 1–2. P. 7–21. DOI: 10.1016/s0027-5107(01)00091-4

[202] Dizdaroglu M. Oxidatively induced DNA damage and its repair in cancer. Mutat Res Rev Mutat Res. 2015;763:212–245. DOI: 10.1016/j.mrrev.2014.11.002

[203] Dizdaroglu M. Oxidatively induced DNA damage and its repair in cancer // Mutat Res Rev Mutat Res. 2015. Vol. 763. P. 212–245. DOI: 10.1016/j.mrrev.2014.11.002

[204] Verhagen H, Aruoma OI, van Delft JH, et al. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo. Food Chem Toxicol. 2003;41(5):603–610. DOI: 10.1016/s0278-6915(03)00025-5

[205] Verhagen H., Aruoma O.I., van Delft J.H., et al. The 10 basic requirements for a scientific paper reporting antioxidant, antimutagenic or anticarcinogenic potential of test substances in in vitro experiments and animal studies in vivo // Food Chem Toxicol. 2003. Vol. 41. No. 5. P. 603–610. DOI: 10.1016/s0278-6915(03)00025-5

[206] Durnev AD. Methodological aspects of studies of chemical mutagenesis modification. Byulleten’ eksperimental’noj biologii i mediciny. 2008;146(9):281–287. (In Russ.) DOI: 10.1007/s10517-008-0273-5

[207] Дурнев А.Д. Методологические аспекты исследований по модификации химического мутагенеза // Бюллетень экспериментальной биологии и медицины. 2008. Т. 146, № 9. С. 281–287. DOI: 10.1007/s10517-008-0273-5

[208] Durnev AD. Antimutagenesis and antimutagens. Human Physiology. 2018;44(3):116–137. (In Russ.) DOI: 10.7868/S013116461803013

[209] Дурнев А.Д. Антимутагенез и антимутагены // Физиология человека. 2018. Т. 44, № 3. С. 116–137. DOI: 10.7868/S013116461803013X