INTERSTRAND DNA CROSS-LINKING INDUCED BY ANTHRACYCLINES IN TUMOR-CELLS

Using a new mild method it is shown for two anthracyclines, Adriamycin (R) and Daunomycin, that these compounds are able to form DNA crosslin ks in HeLa S-3 cells. It was also found that other anthracyclines: Epi rubicin, Rubidazone, Iodorubicin, 3'-deamino-3'-hydroxy-4'-amino-Adria mycin, Aclacinomycin, Marcellomycin, and Cinerubin A, induced crosslin ks in the DNA of HeLa S-3 cells in a concentration-dependent manner. D NA crosslinks formed by five anthracyclines studied, excluding Iodorub icin, were both alkali and thermally unstable. No DNA crosslinking cou ld be detected when the compounds were added to cell lysates in which cellular enzymes had been inactivated. This implies that metabolic act ivation is prerequisite for DNA crosslinking by anthracyclines. The ki netics of DNA crosslinks formation by Adriamycin as well as their remo val from cellular DNA were also studied. The presented results indicat e that all biologically active anthracyclines studied induce DNA cross links, and for two of them DNA crosslinking was observed at growth inh ibitory concentrations.