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  • Title: Stimulation of DNA repair synthesis of rat thymocytes by novobiocin and nalidixic acid in vitro without detectable DNA damage.
    Author: Tempel K, Spath A.
    Journal: Arch Toxicol; 1987 Jun; 60(4):287-92. PubMed ID: 3632353.
    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.
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