Ascorbate-Cu2+ fragments melanoma DNA but not fibroblast DNA into a discrete DNA population.

Ascorbate-Cu2+ shows considerable cytotoxicity for human melanoma cells at a dose which has very little effect on human fibroblasts. Ascorbate itself inhibits DNA synthesis in melanoma cells but does not fragment the parental DNA. However, the combined action of ascorbate-Cu2+ generates fragmentation of the parental DNA due to the induction of alkali-labile bonds in the DNA. In contrast, if DNA polymerase alpha is inhibited by aphidicolin prior to treatment with ascorbate-Cu2+ one cannot detect the fragmentation of the DNA. The generated fragments show a discrete appearance in agarose gel electrophoresis with a single-stranded size of approximately 5 kb. When fibroblasts were analyzed using the same experimental protocol it was not possible to detect the fragmentation of the DNA.