DNA-DAMAGE AND TOPOISOMERASE-II INHIBITION INDUCED BY A BENZOPSORALENDERIVATIVE

The ability of 4-hydroxymethyl-4',5'-benzopsoralen (HMBP) to damage DN A of Chinese hamster ovary cells (CHO) and to inhibit the activity of topoisomerase II in vitro has been studied. This compound is character ized by a fourth ring condensed at the furan-side-in the psoralen mole cule. Contrary to other known furocoumarin derivatives, HMBP induces c hromosomal aberrations in mammalian cells without UVA activation. The lesions induced in the dark by HMBP in DNA were studied by alkaline an d neutral elution in CHO cells; comparable amounts of single-strand br eaks and DNA-protein cross-links as well as the formation of double-st rand breaks were detected. Moreover, HMBP appeared to inhibit the acti vity of mammalian topoisomerase II in vitro, in both the catenation an d the decatenation assay. In these experiments the drug was effective only when it was pre-incubated with DNA substrate. These results are a lso consistent with the cytotoxic and mutagenic activity of HMBP in th e dark, as tested on V79 Chinese hamster cells (V79/HGPRT system).