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  • Title: Comparison of DNA damage and single- and double-strand breakage activities on PM-2 DNA by talisomycin and bleomycin analogs.
    Author: Mirabelli CK, Huang CH, Crooke ST.
    Journal: Cancer Res; 1980 Nov; 40(11):4173-7. PubMed ID: 6162546.
    Abstract:
    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 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.
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