POTENTIATION OF ETOPOSIDE-INDUCED DNA-DAMAGE BY VERAPAMIL IN L-STRAINCELLS IN-VITRO

Verapamil has previously been shown to have enhanced the cytotoxicity of VP-16-213 against malign cell lines in vitro. In this study the cyt otoxic effects of verapamil on the cytotoxicity of etoposide against t ransformed mouse fibroblasts (L-strain cell) were examined. When verap amil was used alone, after 8 hrs, DNA synthesis was increased with res pect to the control cells (p<0.01) and the initial increase of DNA syn thesis was higher with the lowest concentration of verapamil (2 mu g/m l) (p<0.01). In cells that were treated with verapamil and etoposide, after 16 hrs, etoposide cytotoxicity was enhanced and the DNA synthesi s decreased (p<0.01). This enhancement augmented with the increasing d oses of verapamil (p<0.01). Although the initial stimulatory effect of verapamil on the DNA synthesis may have some role in the enhancement of etoposide cytotoxicity, the involvement of some other mechanisms is postulated.