Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations. The level of atypical DNA comets on day 21 after a single administration of streptozotocin increased in the kidneys, but not in the brain, testes, and pancreas. Real-time PCR revealed mtDNA damage in the liver, kidney, and pancreatic cells of mice with streptozotocin-induced diabetes. Thus, these animal models were found to reproduce pathognomic signs of diabetes, hyperglycemia, and nDNA damage; mtDNA damage was also detected.
Similar content being viewed by others
References
Durnev AD, Zhanataev AK, Shreder OV, Seredenina VS. Genotoxic events and diseases. Mol. Med. 2013;(3):3-19. Russian
Møller P, Stopper H, Collins AR. Measurement of DNA damage with the comet assay in high-prevalence diseases: current status and future directions. Mutagenesis. 2020;35(1):5-18. https://doi.org/10.1093/mutage/gez018
Nelson BC, Dizdaroglu M. Implications of DNA damage and DNA repair on human diseases. Mutagenesis. 2020;35(1):1-3. https://doi.org/10.1093/mutage/gez048
Durnev AD, Zhanataev AK, Eremina NV. Genetic Toxicology. Moscow, 2022. Russian.
Eremina NV, Zhanataev AK, Lisitsyn AA, Durnev AD. Genotoxic markers in patients with diabetes mellitus (literature review). Ekol. Genetika. 2021;19(2):143-168. Russian. https://doi.org/10.17816/ecogen65073
Ozerova IV, Taraban KV, Yagubova SS, Ostrovskaya RU. Current state-of-the-art in diabetes modeling. Eksper. Klin. Farmakol. 2017;80(12):35-43. Russian. https://doi.org/10.30906/0869-2092-2017-80-12-35-43
Furman BL. Streptozotocin-induced diabetic models in mice and rats. Curr. Protoc. Pharmacol. 2015;70:5.47.1-5.47.20. https://doi.org/10.1002/0471141755.ph0547s70
King AJ. The use of animal models in diabetes research. Br. J. Pharmacol. 2012;166(3):877-894. https://doi.org/10.1111/j.1476-5381.2012.01911.x
Ostrovskaya RU, Yagubova SS, Zhanataev AK, Anisina EA, Gudasheva TA, Durnev AD. Neuroprotective dipeptide Noopept prevents DNA damage in mice with modeled prediabetes. Bull. Exp. Biol. Med. 2019;168(2):185-190. https://doi.org/10.1007/s10517-019-04681-z
Dabravolski SA, Orekhova VA, Baig MS, Bezsonov EE, Starodubova AV, Popkova TV, Orekhov AN. The Role of Mitochondrial mutations and chronic inflammation in diabetes. Int. J. Mol. Sci. 2021;22(13):6733. https://doi.org/10.3390/ijms22136733
Gureev AP, Shaforostova EA, Starkov AA, Popov VN. Simplified qPCR method for detecting excessive mtDNA damage induced by exogenous factors. Toxicology. 2017;382:67-74. https://doi.org/10.1016/j.tox.2017.03.010
Chen J, Kadlubar FF, Chen JZ. DNA supercoiling suppresses real-time PCR: a new approach to the quantification of mitochondrial DNA damage and repair. Nucleic Acids Res. 2007;35(4):1377-1388. https://doi.org/10.1093/nar/gkm010
Durnev AD, Merkulov VA, Zhanataev AK, Nikitina VA, Voronina ES, Seredenin SB. Methodical recommendations on the evaluation of DNA damage by the method of alkaline gel electrophoresis of individual cells in pharmacological studies. Manual for Preclinical Studies of New Pharmacological Substances. Part I, Mironov AN, ed. Moscow, 2012. P. 115-128. Russian.
Zhanataev AK, Anisina EA, Chayka ZV, Miroshkina IA, Durnev AD. The phenomenon of atypical DNA comets. Cell Tissue Biol. 2017;11(4):286-292. https://doi.org/10.1134/S1990519X17040113
Møller P, Loft S. Statistical analysis of comet assay results. Front. Genet. 2014;5:292. https://doi.org/10.3389/fgene.2014.00292
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 174, No. 9, pp. 337-342, September, 2022
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Zhanataev, A.K., Anisina, E.A., Kulakova, A.V. et al. Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice. Bull Exp Biol Med 174, 349–353 (2023). https://doi.org/10.1007/s10517-023-05717-1
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-023-05717-1