Dose-Response of the Mitomycin C Genotoxic Effect on the ApoE Knockout Mice
- Authors: Asanov M.A.1, Shishkova D.K.1, Poddubnyak A.O.1, Sinitsky M.Y.1, Sinitskaya A.V.1, Khutornaya M.V.1, Ponasenko A.V.1
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Affiliations:
- Research Institute for Complex Issues of Cardiovascular Diseases
- Issue: Vol 109, No 9 (2023)
- Pages: 1273-1281
- Section: ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ
- URL: https://journals.rcsi.science/0869-8139/article/view/229424
- DOI: https://doi.org/10.31857/S0869813923090029
- EDN: https://elibrary.ru/OSJMIA
- ID: 229424
Cite item
Abstract
Polychromic erythrocytes have been accepted as a suitable target for micronucleus (MN) evaluation in both acute and cumulative injury. Mitomycin C (MMC) also has a wide range of genotoxicity, including inhibition of DNA synthesis, clastogenesis and mutagenesis. As an immediate clastogen requiring exclusively intracellular reductive activation, MMS initiates efficient DNA crosslinking. The in vivo micronucleus assay has established itself as a standard assay for evaluating chromosomal genotoxicity in mouse erythrocytes. Most of the studies are focused on the study of acute acute effects, which is caused by high doses of the mutagen. In turn, there are no or very few studies aimed at studying the chronic effects of MMS. The aim of the study is to create a chronic genotoxic effect of MMS without lethal outcome in ApoE–/– mice when selecting the optimal dose of MMS. The design of the study included 6 groups of ApoE–/– mice, two doses of MMC at a concentration of 0.1 and 0.5 mg/kg, single and three doses. Each group consisted of four females and one male. To assess genotoxicity, 1000 polychromic erythrocytes (PChE) extracted from the femoral bone marrow were counted on each sample, PChE with micronuclei were detected, and the proportion of reticulocytes was counted. A dose of 0.5 mg/kg showed a clear cytotoxic effect, expressed in a violation of erythropoiesis, and more precisely in a decrease in the proportion of reticulocytes. In our study, the concentration of the mutagen, namely 0.1 mg/kg, was shown to cause a clear genotoxic effect without reaching the threshold of cytotoxicity. Dose-response studies in rodents can provide useful information on the mechanisms of toxicity and dose selection for long-term toxicity studies.
Keywords
About the authors
M. A. Asanov
Research Institute for Complex Issues of Cardiovascular Diseases
Author for correspondence.
Email: asmaks988@gmail.com
Russia, Kemerovo
D. K. Shishkova
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
A. O. Poddubnyak
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
M. Y. Sinitsky
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
A. V. Sinitskaya
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
M. V. Khutornaya
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
A. V. Ponasenko
Research Institute for Complex Issues of Cardiovascular Diseases
Email: asmaks988@gmail.com
Russia, Kemerovo
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