Detection of DNA-strand breaks in cells treated with F 11782, a catalytic inhibitor of topoisomerases I and II.

F 11782, or 2", 3"-bis pentafluorophenoxyacetyl-4',6'-ethylidene-beta-D glucoside of 4'-phosphate-4'-dimethylepipodophyllotoxin 2N-methyl glucamine salt, is a novel fluorinated lipophylic epipodophylloid which has proven cytotoxic activity in vitro and has shown markedly superior antitumour activity in vivo compared to etoposide in various experimental tumour models. However, the precise mechanism(s) of cytotoxicity of F 11782 remains to be defined. In this study, the DNA damaging activity of F 11782 was investigated in GCT27 and C6S cells using, respectively the fluorescence enhancement assay and the technique of DNA alkaline elution. All the results obtained were consistent with induction of DNA damage by F 11782. No evidence of any stabilisation of DNA-topoisomerase cleavable complexes though was obtained with this catalytic inhibitor. Furthermore, such induction of DNA damage has not been reported with other known catalytic topoisomerase inhibitors and so it appears to be unique to F 11782.