Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells.
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 microg/ml) and then exposed to UV radiation (25 J/m(2)). 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.
Lankoff
A
A
Department of Radiobiology and Immunology, Institute of Biology, Swietokrzyska Academy, ul. Swietokrzyska 15, 25-406 Kielce, Poland. alankoff@pu.kielce.pl
Bialczyk
J
J
Dziga
D
D
Carmichael
W W
WW
Lisowska
H
H
Wojcik
A
A
D000818:Animals; D017209:Apoptosis; D001427:Bacterial Toxins / Q000633:toxicity*; D016466:CHO Cells; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D007700:Kinetics; D008387:Marine Toxins; D052998:Microcystins / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D014466:Ultraviolet Rays
D001427:Bacterial Toxins; D008387:Marine Toxins; D052998:Microcystins; C057862:cyanoginosin LR