LARGE-SCALE FRAGMENTATION OF DNA AND THE DEATH OF TUMOR CELLS BY THE ACTION OF THE BINARY SYSTEM ASCORBIC
ACID-METALLOCOMPLEXES OF COBALT IN VITRO
A.I. Medvedev, V.V. Leschenko
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia;
e-mail: bezlepkin@iteb.ru
High-molecular-weight DNA fragments are the markers of the early stage of apoptosis induced in eukaryotic cells by cytotoxins of different nature. The dynamics of the
development of large-scale DNA fragmentation in K-562 leukemia cells by the action of the antitumor drug, the binary system ascorbic acid-cobalt phthalocyanine within 48 h
of incubation, which correspond to two periods of the doubling of cell number in growing control cultures, have been studied. It was shown that, within the first hours of incubation,
hydrogen peroxide generated by the system induces the formation of DNA fragments from 2200 to 50 kbp long. Later on the cell death accompanied by a decrease in the content
of fragmented DNA is observed. Within 24 h of incubation, part of fragmented DNA remains unrepaired; after 48 h of incubation, a delay or a slowed down proliferation of K-562
cells, which differ from control cells also by a high level of death and a higher content of high-molecular-weight DNA fragments, is observed.
Key words: ascorbic acid, tumor cells, antitumor drugs, hydrogen peroxide, high-molecular-weight dna fragments, genome instability, epigenetic damage
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