title: Stimulation of DNA repair synthesis of rat thymocytes by novobiocin and nalidixic acid in vitro without detectable DNA damage.
abstract: Scheduled (SDS) and unscheduled (UDS) DNA synthesis as well as nucleoid sedimentation was investigated in vitro under the influence of novobiocin (NB) and nalidixic acid (NA) using intact thymic (T-cells) and splenic (S-cells) rat cells and cells which were exposed to X-rays, UV irradiation, methyl methanesulfonate (MMS), and DNA polymerase inhibitors. At concentrations of greater than or equal to 56.25 (S-cells) and greater than or equal to 225 micrograms/ml (T-cells), respectively, NB inhibited SDS in a dose-dependent manner. Within a concentration range of greater than or equal to 225-900 micrograms NB/ml, UDS of S-cells decreased to values far below the tracer ([3H-methyl]-thymidine) incorporation of control cells, whereas UDS of T-cells increased by at least 200%. Within a concentration range of 450-1800 micrograms/ml, NA enhanced SDS and UDS by about 30% in S-cells and by 100% in T-cells. The stimulating activity of NB and/or NA could be eliminated specifically by the DNA polymerase beta inhibitor 2',3'-dideoxythymidine. Enhanced nucleoid sedimentation was observed at NB concentrations greater than or equal to 750 micrograms/ml; S-cells revealed a higher sedimentation rate than T-cells. It is suggested that NB (and NA) influence DNA topology in a rather cell specific manner, stimulating UDS of T-cells by a DNA polymerase beta - dependent repair-like mechanism.
mesh_terms: D000818:Animals; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D009268:Nalidixic Acid / Q000494:pharmacology*; D009675:Novobiocin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D009675:Novobiocin; D009268:Nalidixic Acid; D004259:DNA-Directed DNA Polymerase