Stimulation of DNA repair synthesis of rat thymocytes by novobiocin and nalidixic acid in vitro without detectable DNA damage.
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.
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
D009675:Novobiocin; D009268:Nalidixic Acid; D004259:DNA-Directed DNA Polymerase