Abstract
DNA damage induced in V79 cells by F 11782, or 2″,3″-bis pentafluorophenoxyacetyl-4′, 6′-ethylidene-β-D glucoside of 4′-phosphate- 4′-demethylepipodophyllotoxin 2N-methyl glucamine salt, a novel dual catalytic inhibitor of topoisomerases I and II, was investigated using both alkaline and neutral versions of the comet assay methodology. A comparison was then made of the DNA damage induced by F 11782 with that induced by either etoposide or camptothecin under comparable experimental conditions. The results revealed that F 11782 initially induced less DNA strand breaks that either etoposide or camptothecin and rejoined such breaks more slowly. However, unlike these other drugs, the extent of DNA damage induced by F 11782 increased linearly with time of incubation. F 11782 produced both DNA single- and double-strand breaks without any clear specificity relative to phase of the cell cycle, although proliferating cells were preferentially damaged. The marked time-dependency of induction of DNA strand breaks by F 11782 may serve to explain, at least in part, its major in vivo antitumour activities. © 2000 Cancer Research Campaign http://www.bjcancer.com
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Barret, JM., Hill, B. & Olive, P. Characterization of DNA-strand breakage induced in V79 cells by F 11782, a catalytic inhibitor of topoisomerases. Br J Cancer 83, 1740–1746 (2000). https://doi.org/10.1054/bjoc.2000.1514
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DOI: https://doi.org/10.1054/bjoc.2000.1514