Inhibition of DNA repair in ultraviolet-irradiated human cells by hydroxyurea.
The effect on DNA repair in ultraviolet-irradiated human skin fibroblasts by hydroxyurea has been examined in this study using three independent methods for measuring DNA repair:the 5-bromodeoxyuridine photolysis assay which measures DNA repair replication, chromatographic measurement of thymine-containing dimers, and measurement of specific ultraviolet-endonuclease-sensitive sites in irradiated DNA. Little effect of hydroxyurea was observed at the concentration of 2 mM, which is often used to inhibit semiconservative DNA synthesis; however, 10 mM hydroxyurea resulted in marked inhibition (65--70%) of excision repair. This inhibition was accompanied by a possible doubling in the size of the repaired region. The accumulation of large numbers of single-strand breaks following ultraviolet irradiation and hydroxyurea incubation seen by other investigators was not observed with the normal skin fibroblasts used in this study. A comparison of hydroxyurea effects on the different DNA repair assays indicates inhibition of one step in DNA repair also results in varying degrees of inhibition of other steps as well.
D001973:Bromodeoxyuridine / Q000494:pharmacology; D002478:Cells, Cultured; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000528:radiation effects; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
D001973:Bromodeoxyuridine; D006918:Hydroxyurea