N-Trifluoroacetyladriamycin-14-valerate and adriamycin induced DNA damage in the RPMI-6410 human lymphoblastoid cell line

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Abstract
The adriamycin and N-trifluoroacetyladriamycin-14-valerate (AD-32) [antitumor agent] induced DNA cross-linking and breakage in human RPMI-6410 cells was compared using the alkaline elution technique of Kohn et al. At comparable growth-inhibitory concentrations both adriamycin and AD-32 caused DNA cross-linking. Treatment with proteinase-K showed this cross-linking to be mainly DNA-protein in character. Proteinase-K treatment also revealed that both drugs caused either single-strand DNA breaks or increased alkaline sensitivity. With adriamycin the degree of cross-linking and breakage was dose related over the range studied (0.05-0.4 .mu.g/ml), whereas with AD-32 there appeared to be a saturation of both effects at concentrations in excess of 3 .mu.g/ml. With both drugs the extent of cross-linking and breakage was maximal at the end of the drug exposure. Apparently, AD-32 or some metabolite of it binds to DNA and this binding leads to DNA damage that is similar to that caused by adriamycin. These AD-32 results are somewhat surprising in light of earlier model studies showing that AD-32 does not bind to isolated DNA.