Coincidence in fragile site expression with fluorodeoxyuridine and bromodeoxyuridine

Fragile site expression induced by 10 micrograms/ml or 20 micrograms/ml fluorodeoxyuridine (FudR) and 25 micrograms/ml or 50 micrograms/ml bromodeoxyuridine (BrdU) was studied in lymphocyte cultures of six healthy individuals. A significant decrease in mitotic indexes in respect to control cultures was observed with both FudR concentrations used. The cells showing chromosome aberrations and the total number of cytogenetic alterations were significantly increased both in FudR (p less than 0.001) and BrdU (25 micrograms/ml) (p less than 0.05) treated cultures with respect to the control culture. A site showing a gap or a break was defined as fragile if it appeared in 1% of the cells analyzed and in at least three of the six individuals studied with the same culture treatment. Using these criteria, fragile sites 4q31, 5q15, 6p22, 7p13, 7q32, 13q21, and 14q24 were induced in different proportions by both chemical agents. Although these drugs act via different mechanisms, they both substitute for thymidine in DNA. Our findings suggest that FudR is a more potent common fragile site inducer than BrdU.