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Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells
Authors:A Lankoff  J Bialczyk  D Dziga  WW Carmichael  H Lisowska  A Wojcik  
Institution:

aDepartment of Radiobiology and Immunology, Institute of Biology, Swietokrzyska Academy, ul. Swietokrzyska 15, 25-406 Kielce, Poland

bDepartment of Plant Physiology and Development, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland

cDepartment of Biological Sciences, Wright State University, Dayton, OH, USA

dDepartment of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Warsaw, Poland

Abstract:Microcystin-LR (MC-LR), a potent inhibitor of PP1 and PP2A protein phosphatases, is related to tumor promotion and initiation. Although the genotoxic properties of this toxin have been extensively investigated with a variety of non-mammalian and mammalian test systems, the existing results are contradictory. Based on our previous results regarding the impact of MC-LR on the processes of DNA repair we decided to examine in greater detail its effect on the capacity of nucleotide excision repair (NER). CHO-K1 cells were pre-treated with increasing doses of MC-LR (1, 10 and 20 μg/ml) and then exposed to UV radiation (25 J/m2). Apoptosis was analyzed to exclude the possibility of false positive results in the comet assay. The results suggest that MC-LR targets the nucleotide excision repair mechanisms by interference with the incision/excision phase as well as the rejoining phase of NER and leads to an increased level of UV-induced cytogenetic DNA damage in CHO-K1 cells.
Keywords:Microcystin-LR  UV radiation  DNA damage  Nucleotide excision repair  Micronuclei  Apoptosis  CHO-K1 cells
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