SENSITIZATION TO DNA-DAMAGE BY OKADAIC ACID OF BROMODEOXYURIDINE INVOLVES UNEQUAL EFFECTS ON MELANOMA CELL-ADHESION AND DIFFERENTIATION

Because melanoma tumors originate partly from excessive UV exposure bu t become relatively resistant to radiation, we have now compared the e ffects of okadaic acid, a phosphatase inhibitor, with that of the thym idine analog bromodeoxyuridine as sensitizers of DNA damage in B16 mel anoma, We now show that 25 nM okadaic acid promotes DNA fragmentation in B16 melanoma, increasing cell detachment as well as pigmentation, a characteristic of melanocytic cell differentiation. At lower levels, okadaic acid synergizes with UV exposure to increase DNA fragmentation , Although bromodeoxyuridine also caused DNA damage, it did not increa se pigmentation and it suppressed cell detachment, Okadaic acid was al so more effective in promoting DNA laddering in growing versus quiesce nt melanocytes, Because DNA damaging effects of okadaic acid are media ted by different pathways from those used by nucleoside analogs, like bromodeoxyuridine, we propose their concurrent effect with radiation a s sensitizers to DNA damage.