The induction of fragile sites on human chromosomes has been demonstrated under various conditions that cause thymidylate stress, including exposure to
uridine. In this study, we examined common fragile site expression by initially exposing peripheral lymphocytes to
uridine, followed by repair of the fragile sites with media containing various concentrations of
thymidine. Lymphocytes were cultured in medium 199 with 2 mM
uridine. At 0.5, 1, 2, 3, 8, 10, 12, and 18 h before harvest, the
uridine medium was removed and replaced by medium containing
thymidine at various concentrations. Our results demonstrate that the effect of
uridine on
chromosome fragility can be reversed by low concentrations of
thymidine (2 microM up to 200 microM) and the "rescuing" effect of
thymidine can be achieved if the cells were treated prior to 2-3 h before harvest. No repair was found if
thymidine was added to culture within 2 h prior to harvesting, suggesting that packing of chromosomes is also an important factor in the expression and repair of fragile sites.