EFFECTS OF UKRAIN ON THE ACTIVITIES OF DNA-NICKING ENZYMES

VOTRIN I.I.,^†1 VOLTCHEK I.V.,² KUROCHKIN S.N.,³ KOLOBKOV S.L.⁴

1) Institute of Biological and Medical Chemistry, Russian Academy of Medical Sciences, Moscow, Russia.
2) Terra Medica, Zanevsky, St. Petersburg, Russia.
3) Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
4) Center of Medical Biotechnology, Ministry of Health, Moscow, Russia.

Address for correspondence: I.V. Voltchek, Terra Medica, Zanevsky pr., 1, of. 255, St. Petersburg 195196, Russia.

Summary: We studied the effects of Ukrain, a novel antitumor drug, on the activities of calcium, magnesium-dependent endonuclease (CME) and manganese-dependent endonuclease (MnDE) in rat liver nuclei, the activity of topoisomerase I assessed by pUC19 plasmid relaxation and CME activity in the nuclei of lymphocytes from colon cancer patients. Ukrain was found to exert a dose-dependent inhibiting effect on both CME and MnDE, similar to that exerted by erythropoietin, which was used as a reference preparation. Both Ukrain and erythropoietin also caused dose-dependent inhibition of topoisomerase I activity. The influence of Ukrain on CME activity in the nuclei of the lymphocytes of colon cancer patients was differential, depending on treatment efficacy. The results suggest that DNA-nicking enzymes may be a target of Ukrain and may mediate its antitumor effects.