Synergism between aphidicolin and adenoviruses in the induction of breaks at fragile sites on human chromosomes

Infection of human embryonic kidney cells with adenoviruses results in the induction of gaps and breaks in cell chromosomes. With adenovirus type 12, cytogenetic damage is known to occur primarily at fragile sites on chromosomes 1 and 17. We have mapped adenovirus type 5-induced breaks and have observed that, although they occur on all chromosomes, they are localized primarily on bands where fragile sites have been mapped. The susceptibility of fragile sites to adenovirus led us to investigate their expression upon combined treatments with virus and aphidicolin, a frequently used inducer of fragile sites. Under these experimental conditions, the frequency of damage at all sites was found to increase significantly, and the magnitude of such increases indicated a synergistic effect between drug and virus.