Mutagenesis Advance Access published online on January 24, 2006
Mutagenesis, doi:10.1093/mutage/gel002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Radiobiology and Immunology, Institute of Biology, Swi
* To whom correspondence should be addressed. The genotoxic activity of microcystin-LR (MC-LR) is a matter of debate. MC-LR is known to be a phosphatase inhibitor and it may be expected that it is involved in the regulation of the activity of DNA-dependent protein kinase (DNA-PK), the key enzyme involved in the repair of radiation-induced DNA damage. We studied the effect of MC-LR on the repair capacity of radiation-induced DNA damage in human lymphocytes and human glioblastoma cell lines MO59J and MO59K. A dose of 0.5 µg/ml of MC-LR was chosen because it induced very little early apoptosis which gives no false positive results in the comet assay. Human lymphocytes in G0-phase of the cell cycle were pre-treated with MC-LR for 3 h and irradiated with 2 Gy of gamma radiation. The kinetics of DNA repair was assessed by the comet assay. In addition the frequencies of chromosomal aberrations were analysed. The pre-treatment with MC-LR inhibited the repair of radiation-induced damage and lead to enhanced frequencies of chromosomal aberrations including dicentric chromosomes. The results of a split-dose experiment, where cells were exposed to two 1.5 Gy doses of radiation separated by 3 h with or without MC-LR, confirmed that the toxin increased the frequency of dicentric chromosomes. We also determined the effect of MC-LR and ionizing radiation on the frequency of
Received August 23, 2005
Revised December 18, 2005
Accepted January 2, 2006
Article
The repair of gamma-radiation-induced DNA damage is inhibited by microcystin-LR, the PP1 and PP2A phosphatase inhibitor
A. Lankoff 1 *,
J. Bialczyk 2,
D. Dziga 2,
W. W. Carmichael 3,
I. Gradzka 4,
H. Lisowska 1,
T. Kuszewski 5,
S. Gozdz 5,
I. Piorun 1,
and
A. Wojcik 6
tokrzyska Academy, Kielce, Poland
2 Department of Plant Physiology and Development, Faculty of Biotechnology, Jagiellonian University, Kraków, Poland
3 Department of Biological Sciences, Wright State University, Dayton, OH, USA
4 Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Warsaw, Poland
5 Department of Medical Physics, Swietokrzyskie Oncology Center, Kielce, Poland
6 Department of Radiobiology and Immunology, Institute of Biology, Switokrzyska Academy, Kielce, Poland; Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Warsaw, Poland
A. Lankoff, E-mail: alankoff{at}pu.kielce.pl
Abstract 
-H2AX foci. The pre-treatment with MC-LR resulted in reduced numbers of -H2AX foci in irradiated cells. In order to elucidate the impact of MC-LR on DNA-PK we examined the kinetics of DNA repair in human glioblastoma MO59J and MO59K cells. Both cell lines were exposed to 10 Gy of X-rays and DNA repair was analysed by the comet assay. A strong inhibitory effect was observed in the MO59K but not in the MO59J cells. These results indicate that DNA-PK might be involved in DNA repair inhibition by MC-LR.
CiteULike 
Connotea 
Del.icio.us What's this?