Characterization of DNA-strand breakage induced in V79 cells by F 11782, a catalytic inhibitor of topoisomerases.
DNA damage induced in V79 cells by F 11782, or 2",3"-bis pentafluorophenoxyacetyl-4',6'-ethylidene-beta-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.
Barret
J M
JM
Division de Cancérologie, Centre de RecherchePierre Fabre, 17 avenue Jean Moulin, Castres, 81100, France.
Hill
B T
BT
Olive
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PL
D000818:Animals; D002166:Camptothecin / Q000494:pharmacology; D002460:Cell Line; D020552:Comet Assay; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D059004:Topoisomerase I Inhibitors
D009281:Naphthalenes; D011714:Pyrans; D059004:Topoisomerase I Inhibitors; D005047:Etoposide; D004247:DNA; D004264:DNA Topoisomerases, Type I; C405744:tafluposide; D002166:Camptothecin