This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mirabelli, C. K. Articles by Crooke, S. T. Search for Related Content PubMed PubMed Citation Articles by Mirabelli, C. K. Articles by Crooke, S. T.

Comparison of DNA Damage and Single- and Double-Strand Breakage Activities on PM-2 DNA by Talisomycin and Bleomycin Analogs¹

Bristol-Baylor Laboratory, Department of Pharmacology, Baylor College of Medicine, Texas Medical Center, Houston, Texas 77030 [C. K. M., C. H. H., S. T. C.], and the Bristol Laboratories, Syracuse, New York 13201 [S. T. C.]

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, S_2b, and S_10b. 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 S_2b and S_10b 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.

¹ This work was supported in part by a grant from the Bristol Laboratories and by a grant (CA-10893-P-12) from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 5/16/80. Accepted 8/11/80.