Single- and double-strand breakage of isolated PM-2 DNA by structural analogs of the glycopeptide antitumor antibiotics bleomycin (BLM) and talisomycin (TLM) was investigated. Breakage of PM-2 DNA was determined by two systems: an ethidium bromide fluorescence assay; and agarose gel electrophoresis. The fluorescence assay, which measures total breakage of DNA including single- and double-strand breakage and alkaline labile damage, showed that the BLM's, A2 and B2 induced more total DNA breakage

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... than did the TLM's A, B, S2b, and S10b. As measured by the comparison of the concentration of analog required to cause 50% breakage of superhelical DNA, BLM's A2 and B2 were 10 times more active than TLM's S2b and S10b and 25 times more active than TLM's A and B. Gel electrophoresis, which measures the extent of both single- and double-strand breakage of DNA, showed that at equivalent levels of breakage of superhelical DNA each of the TLM's caused more double-strand breakage of DNA than did the BLM's. Thus, the structural alterations near the bithiazole in the TLM's, which distinguish them structurally from the BLM's, result in a reduction of the total PM-2 DNA breakage activity and enhanced production of double-strand breaks relative to single-strand breaks by TLM when compared to BLM.