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Effects of an antimutagen of 1,4-dihydropyridine series on cell survival and DNA damage in L5178Y murine sublines

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EN
Abstrakty
EN
In a series of studies it was shown that 1,4-dihydropyridine derivatives (1,4-DHP) show antimutagenic and anticlastogenic properties and accelerate repair of oxidant and ionising radiation generated DNA damage. Here, effects of one of 1,4-DHP compounds (sodium 3,5-bis-ethoxycarbonyl-2,6-dimethyl-1,4-dihydropyridine-4-carboxylate denoted as DHP) in X-irradiated L5178Y cells (murine lymphoma sublines, LY-R and LY-S) are reported. DHP treatment 1 h before, during and after X-irradiation gave a radioprotective effect in double strand break (DSB) repair competent LY-R cells: there was an increase in post-irradiation proliferation and cell viability as well as a slight acceleration of break rejoining as measured by the neutral comet assay. In the radiosensitive LY-S cells with impaired non-homologous end-joining system, the radioprotective effect was seen as enhanced growth and viability. There was, however, no effect on the DSB repair rate. Notably, there was no dependence of the biological effects on DHP concentration in the range of concentrations studied (1 nM - 100 mM), suggesting an all-or-none effect, as in cellular signaling induction observed in radioadaptation or bystander effect. We assume that DHP acts by decreasing fixation of radiation inflicted DNA damage, among others, by increasing the rate of DNA repair and enhancing the efficiency of checkpoint control. Direct confirmation of this assumption is necessary.
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141--146
Opis fizyczny
Bibliogr. 23 poz., rys.
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autor
autor
autor
autor
  • Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Str., Minsk 220072, Republic of Belarus, izasz@orange.ichtj.waw.pl
Bibliografia
  • 1. Azzam EI, De Toledo SM, Little JB (2004) Stress signaling from irradiated to non-irradiated cells. Curr Cancer Drug Targets 4:53−64
  • 2. Broome EJ, Brown DL, Mitchel REJ (2002) Dose responses for adaption to low doses of Co-60 gamma rays and H-3 beta particles in normal human fibroblasts.Radiat Res 158:181−186
  • 3. Dalivelia OV, Savina NV, Kuzhir TD, Goncharova RI (2005) DNA-repair modulation using derivatives of 1,4-dihydroisonicotinic acid as an example. Tsitol Genet 39:62−72 (in Russian)
  • 4. Fenech M, Morley AA (1986) Cytokinesis-block micronucleus method in human lymphocytes: effect of in vivoageing and low dose X-irradiation. Mutat Res 161:193−198
  • 5. Floersheim GL (1992) Calcium antagonists protect mice against lethal doses of ionizing radiation. Br J Radiol 65:1025−1029
  • 6. Floersheim GL (1993) Radioprotective effects of calcium antagonists used alone or with other types of radioprotectors. Radiat Res 133:80−87
  • 7. Goel HC, Ganguly SK, Prasad J, Jain V (1996) Radioprotective effects of diltiazem on cytogenetic damage and survival in gamma ray exposed mice. Indian J Exp Biol 34:1194−1200
  • 8. Goncharova RI, Kuzhir TD (1989) The comparative study of the antimutagenic effects of antioxidants on chemical mutagenesis in Drosophila melanogaster. Mutat Res 214:257−265
  • 9. Goncharova R, Zabrejko S, Dalivelya O, Kuzhir T (2001)Anticlastogenicity of two derivatives of 1,4-dihydroisonicotinic acid in mouse micronucleus test. Mutat Res 496:129−135
  • 10. Hallahan DE, Bleakman D, Virudachalam S et al. (1994) The role of intracellular calcium in the cellular response to ionizing radiation. Radiat Res 138:392−400
  • 11. Kuzhir TD, Dalivelia OV, Savina NV (1999) Modification of the repair processes in chemical mutagenesis in Drosophila melanogaster. Genetika 35:919−924 (in Russian)
  • 12. Kuzhir TD, Goncharova RI (1997) Some effects of 1,4-dihydroisonicotinic acid derivatives on repair pathways involved in chemical mutagenesis (abstract). Biochem Soc Trans 25:139S
  • 13. Lukas J, Lukas C, Bartek J (2004) Mammalian cell cycle checkpoints: signalling pathways and their organization in space and time. DNA Repair 3:997−1007
  • 14. Mothersill CE, Moriarty MJ, Seymour CB (2004) Radiotherapy and the potential exploitation of bystander effects. Int J Radiat Oncol Biol Phys 58:575−579
  • 15. Ryabokon NI, Goncharova RI, Duburs G, Rzeszowska-Wolny J (2004) The 1,4-dihydropyridine derivative promotes DNA repair through stimulation of poly(ADPribosylation).In: Gliwice Scientific Meetings 2004. Bookof abstracts, p 62
  • 16. Ryabokon NI, Goncharova RI, Duburs G, Rzeszowska-Wolny J (2005) A 1,4-dihydropyridine derivative reduces DNA damage and stimulates DNA repair in human cells in vitro. Mutat Res 587:52−58
  • 17. Szumiel I (2003) The bystander effect: is reactive oxygen species the driver? Nukleonika 48:113−120
  • 18. Szumiel I (2005) Adaptive response: stimulated DNA repair or decreased damage fixation? Int J Radiat Biol 81:233−241
  • 19. Szumiel I (2005) L5178Y sublines: a look back from 40 years. Part 1: general characteristics. Int J Radiat Biol 81:339−352
  • 20. Szumiel I (2005) L5178Y sublines: a look back from 40 years. Part 2: response to ionizing radiation. Int J Radiat Biol 81:353−365
  • 21. Todd DG, Mikkelsen RB (1994) Ionizing radiation induces a transient increase in cytosolic free [Ca2+] in human epithelial tumor cells. Cancer Res 54:5224−5230
  • 22. Vartanian LP, Ivanov EV, Vershinina SF et al. (2004) Antineoplastic effect of glutapyrone in continual gammairradiation of rats. Radiats Biol Radioecol 44:198−201 (in Russian)
  • 23. Wojewódzka M, Buraczewska I, Kruszewski M (2002) A modified neutral comet assay: elimination of lysis at high temperature and validation of the comet assay with antisingle-stranded DNA antibody. Mutat Res 518:9−20
Typ dokumentu
Bibliografia
Identyfikator YADDA
bwmeta1.element.baztech-article-BUJ5-0003-0004
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