Arabinofuranosyl nucleosides induce common fragile sites

The capacities for fragile site induction of three inhibitors of semiconservative DNA synthesis and DNA repair synthesis, aphidicolin, arabinofuranosyl cytosine, and arabinofuranosyl adenosine were compared. Aphidicolin is known to induce type 4 fragile sites, the largest recognized group of common fragile sites. Although the modes of action of these inhibitors vary, both arabinofuranosyl analogs induce type 4 aphidicolin-sensitive fragile sites. An analysis of variance demonstrates that the three inhibitors are not equally capable of inducing significant breakage (P less than 0.01) at all type 4 fragile sites. Induction of type 4 fragile sites appears to be a general consequence of inhibition of DNA polymerization.