The effect of mitotic inhibitors on formation and repair of DNA breaks was studied in cultured fibroblasts from patients with Down syndrome in order to investigate the hypothesis that the karyotyping procedure itself may play a role in the increased chromosome breakage seen in these cells after gamma radiation exposure. Using the nondenaturing elution and alkaline elution techniques to examine fibroblasts from Down syndrome patients and from controls, no specific abnormalities in Down syndrome cells could be detected after exposure to mitotic inhibitors, including rate and extent of elution of DNA from filters as well as repair of radiation-induced DNA breaks. In both normal and Down syndrome cell strains, however, exposure to mitotic inhibitors was associated with a decrease in cellular DNA strand size, suggesting the presence of drug-induced DNA strand breaks. The mechanism of increased chromosome sensitivity of Down syndrome cells to gamma radiation remains unknown.
Bibliographical noteFunding Information:
This work was supported in part by grant EY04612-01 from the U.S. National Eye Institute and the Viking Children's Fund. William G. Woods is the recipient of a Junior Faculty Clinical Fellowship from the American Cancer Society.
- (Human fibroblast)
- DNA damage
- DNA repair
- Down syndrome
- Mitotic inhibitor
- Radiation damage