NUKLEONIKA 2006, 51(3):141-146

EFFECTS OF AN ANTIMUTAGEN OF 1,4-DIHYDROPYRIDINE SERIES ON CELL SURVIVAL AND DNA DAMAGE IN L5178Y MURINE SUBLINES

Olga Dalivelya1, Natalya Savina1, Tatyana Kuzhir1, Iwona Buraczewska2, Maria Wojewódzka2, Irena Szumiel2

1 Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Str., Minsk 220072, Republic of Belarus
2 Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, 16 Dorodna Str., 03-195 Warsaw, Poland


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.