Influence of reduced glutathione on end-joining of DNA double-strand breaks: Cytogenetical and molecular approach

Publication date: Available online 9 November 2016 Source:Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Author(s): Nitin Ghoshal, Sheetal Sharma, Atanu Banerjee, Sillarine Kurkalang, Sathees C Raghavan, Anupam Chatterjee Radiation induced DNA double-strand breaks (DSB) are the major initial lesions whose misrejoining may lead to exchange aberrations. However, the role of glutathione (GSH), a major cellular thiol, in regulating cell’s sensitivity to DNA damaging agents is not well understood. Influence of endogenous GSH on the efficiency of X-rays and bleomycin (Blem) induced DNA DSBs end-joining has been tested here cytogenetically, in human lymphocytes and Hct116 cells. In another approach, oligomeric DNA (75bp) containing 5′-compatible and non-compatible overhangs mimicking the endogenous DSB were for rejoining in presence of cell-free extracts from cells having different endogenous GSH levels. Frequency of aberrations, particularly exchange aberrations, was significantly increased when Blem was combined with radiation. The exchange aberration frequency was further enhanced when combined treatment was given at 4°C since DNA lesions are poorly repaired at 4°C so that a higher number of DNA breaks persist and interact when shifted from 4°C to 37°C. The exchange aberrations increased further when the combined treatment was given to Glutathione-ester (GE) pre-treated cells, indicating more frequent rejoining of DNA lesions in presence of ...

Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - November 9, 2016 Category: Cytology Source Type: research