DNA-PROTECTIVE ACTIVITY OF NEW RIBONUCLEOTIDE REDUCTASE INHIBITORS

The DNA-protective activity of hydroxyurea (HU) and novel ribonucleoti de reductase (RR) inhibitors amidox (AX), didox (DX) and trimidox (TX) was examined using hydrogen peroxide as the DNA-damaging agent. The e xposure of superspiralized plasmid DNA molecules (pBR 322) to H2O2 und er precisely defined in vitro conditions initiates a change in DNA top ology (DNA form I relaxes to DNA form II). This electrophoretically mo nitored change in the plasmid DNA topology is related to the induction of ss-DNA breaks and corresponds with DNA exposition to free radicals . The inhibition of DNA relaxation (the prevention of DNA damage induc ed by hydrogen peroxide) depended on the free radical scavenging capac ity of the dugs investigated HU exterted DNA protective activity at a concentration of 4 mM, AX at concentration of 1 mu M, TX at a concentr ation of 5 mu M and DX at a concentration of 25 mu M (the free radical scavenging activity increases from HU to AX in following manner: HU< <DX< TX<AX). It can be concluded that the new synthetic RR-inhibitor A X which is being investigated at the preclinical level as a potential anti-cancer drug possess the highest capacity for scavenging of free r adicals.