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Inhibition of nucleotide excision repair (NER) by microcystin-LR in CHO-K1 cells
A Lankoff1, J Bialczyk, D Dziga
1Department of Radiobiology and Immunology, Institute of Biology, Swietokrzyska Academy, ul. Swietokrzyska 15, 25-406 Kielce, Poland. alankoff@pu.kielce.pl
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.
Insights
Microcystin-LR (MC-LR) impairs DNA repair mechanisms, specifically nucleotide excision repair (NER), in cells exposed to UV radiation. This toxin increases UV-induced DNA damage, highlighting its genotoxic potential.
Area of Science:
- Environmental toxicology
- Molecular toxicology
- Cellular biology
Background:
- Microcystin-LR (MC-LR) is a cyanotoxin that inhibits protein phosphatases PP1 and PP2A.
- MC-LR is linked to tumor promotion and initiation, but its genotoxic effects remain debated.
- Previous studies indicated MC-LR impacts DNA repair processes.
Purpose of the Study:
- To investigate the effect of MC-LR on the nucleotide excision repair (NER) capacity in cells.
- To determine if MC-LR interferes with specific phases of the NER pathway.
- To assess the impact of MC-LR on UV-induced DNA damage.
Main Methods:
- CHO-K1 cells were treated with varying concentrations of MC-LR (1, 10, 20 microg/ml).
- Cells were subsequently exposed to UV radiation (25 J/m(2)).
- Apoptosis was analyzed to validate comet assay results for DNA damage assessment.
Main Results:
- MC-LR interferes with both the incision/excision and rejoining phases of NER.
- The toxin leads to a higher level of UV-induced cytogenetic DNA damage in CHO-K1 cells.
- Apoptosis analysis confirmed the reliability of the observed DNA damage.
Conclusions:
- MC-LR compromises the cellular capacity to repair UV-induced DNA damage via NER.
- The toxin's interference with NER highlights its genotoxic potential and contribution to DNA damage.
- These findings provide a deeper understanding of MC-LR's molecular mechanisms in genotoxicity.
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