Study of clustered DNA lesions in the liver in acute toxic injury

Abstract

Objective: to test and optimize a method for detecting clustered DNA lesions with an assessment of the quantitative characteristics of hepatic changes using an experimental model of acute toxic hepatitis.Material and methods: Laboratory C57Bl/6 mice at the age of 10 weeks were used for the study. Acute toxic liver injury was induced by means of a single intraperitoneal injection of 30 % CCI4 solution in olive oil. The withdrawal of the animals from the experiment was made after 72 hours. For the detection of clustered DNA lesions, a liver fragment was resected.Results. The electrophoretic parameters which are the most optimal for obtaining primary data for the subsequent calculation of the number of clustered DNA lesions have been proposed. The number of clusters in the DNA samples from the animals of the control group is significantly lower than in the experimental group and amounts to 54.80 [37.65; 59.24] and 76.82 [60.95; 92.41] APE1 clusters per million bp., respectively.Conclusion. Successful testing and optimization of the OCDL method for the detection of clustered lesions in liver DNA have been performed. The study has shown an increase in the number of APE1 clusters and double-strand breaks in the DNA of the C57Bl laboratory mice with induced acute toxic hepatitis, which indicates significant derangement of DNA integrity and a high risk of developing progressive liver diseases in its toxic damage.