[Nicotinamide decreases DNA destabilization in K562 cells treated with AlF(-4)]

Using trypan blue exclusion test it has been shown that a 18 hour incubation of human erythromyeloleukosis cell line K562 together with AlF(-4) (10 mM NaF + 20 mkM AlCl3) reduced cell proliferation and survival. However, the latter parameter did not change during 4 hours of incubation. Nevertheless, AlF(-4) increased fragmentation of 3H-thymidine-labelled DNA by 2-4 times. This effect may be suppressed by cultivation of cells with 20 mkM nicotinamide (inhibitor of poly(ADP-ribose)polymerase enzyme). We found that incubation of K562 and YAC-1 cells with 10 mM nicotinamide for 24 hours much reduced their susceptibility to non-MHC-restricted lysis by rat spleen cells. This effect may be induced by a share of intracellular NAD+ and NADH from destroyed K562 cells; their concentration in cells increased under the influence of nicotinamide by 3 times, but this effect should be the least because in these conditions nicotinamide does not influence the survival of K562 cells. The effect of nicotinamide in both cases may be explained by suppression of poly(ADP-ribose)polymerase activity and, thus, the rate of DNA reparation. Analysis of AlF(-4) and nicotinamide effects on the K562 cells enables us to suppose that suppression of the K562 proliferation by tetrafluoroaluminate results in accumulation of reversed damages of DNA.