Characterization of DNA-strand breakage induced in V79 cells by F 11782, a catalytic inhibitor of topoisomerases

Br J Cancer. 2000 Dec;83(12):1740-6. doi: 10.1054/bjoc.2000.1514.


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.

MeSH terms

  • Animals
  • Camptothecin / pharmacology
  • Cell Line
  • Comet Assay
  • DNA / drug effects*
  • DNA / genetics
  • DNA Damage*
  • DNA Topoisomerases, Type I / metabolism
  • Dose-Response Relationship, Drug
  • Etoposide / pharmacology
  • Naphthalenes / pharmacology*
  • Pyrans / pharmacology*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / metabolism
  • Time Factors
  • Topoisomerase I Inhibitors*


  • Naphthalenes
  • Pyrans
  • Topoisomerase I Inhibitors
  • Etoposide
  • DNA
  • DNA Topoisomerases, Type I
  • tafluposide
  • Camptothecin