DOLASTATIN-10 INDUCES POLYPLOIDY, TELOMERIC ASSOCIATIONS AND APOPTOSIS IN A MURINE MELANOMA CELL-LINE

Our purpose was to study the effects of dolastatin-10 (Dol-10) on chro mosome morphology, telomeric associations, induction of polyploidy and cell death in a metastatic murine melanoma cell line, K1735 clone X-2 1. Murine melanoma cells were treated with various concentrations (10 ng/ml, 100 ng/ml and 1000 ng/ml) of Dol-10 for 4, 24 and 72 h continuo usly and harvested immediately without recovery. In another set of exp eriments, cells were treated for 4 h with the same concentrations, was hed with prewarmed medium and then allowed to recover in drug-free med ium for 24 h and subsequently harvested. Our preliminary results indic ated: i) a drug-mediated increase in the frequency of metaphases, with telomeric associations resulting in multicentric and ring configurati ons; ii) induction of clumping in metaphase chromosomes; iii) inductio n of polyploidy as a result of endoreduplication; iv) formation of mic ronucleated cells; and v) induction of cell death. These observations indicated that Dol-10 could be a potent antineoplastic drug against ma lignant melanoma. In addition to its reported interaction with cell mi crotubules, the mechanism of action of Dol-10 may be mediated through the loss of telomeric repeats and induction of chromosome aberrations.