Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells

Toxicon. 2006 Dec 15;48(8):957-65. doi: 10.1016/j.toxicon.2006.08.003. Epub 2006 Aug 12.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Bacterial Toxins / toxicity*
  • CHO Cells
  • Comet Assay
  • Cricetinae
  • Cricetulus
  • DNA Damage
  • DNA Repair / drug effects*
  • DNA Repair / radiation effects
  • Kinetics
  • Marine Toxins
  • Microcystins / toxicity*
  • Micronuclei, Chromosome-Defective / drug effects
  • Ultraviolet Rays

Substances

  • Bacterial Toxins
  • Marine Toxins
  • Microcystins
  • cyanoginosin LR