Differences between thymic and splenic cells of the rat: biochemical and physico-chemical investigations in vitro on DNA topoisomerase II--inhibitors and thiyl radicals.
Interactions of novobiocin (NB) and nalidixic acid (NA) with thiols were investigated in vitro in thymic (T-) and splenic (S-) cells of the rat, by determining nucleic acid synthesis as well as nucleoid sedimentation and viscosity of alkaline cell lysates. In T-cells NB, at concentrations of 0.35-1.4 mM, increased unscheduled DNA synthesis (UDS) and RNA synthesis (RNS), whereas S-cells underwent a dose-dependent inhibition of UDS and RNS following exposure to NB at concentrations > 0.7 mM. Combining NA and thiols (e.g., dithiothreitol) resulted in a slight stimulation of UDS in S-cells and in a highly significant increase of UDS in T-cells ascribed to a depletion of the cellular thymidine pool. In both cell types, neither NB nor NA exerted a significant effect on thiol-induced DNA damage. At a concentration of 1.4 mM, NB increased the viscosity of alkaline T-cell lysates; the opposite effect was observed in S-cells. From these results as well as from previous investigations we conclude that T- and S-cells differ in their state of chromatin conformation. This interpretation offers a simple model for the study of the influence of chromatin structure on cell-specific physico-and/or chemico-biological interactions.
Tempel
K
K
Institut für Pharmakologie, Toxikologie und Pharmazie, Universität München, Bundesrepublik Deutschland.
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D006690:Bisbenzimidazole / Q000494:pharmacology; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004229:Dithiothreitol / Q000494:pharmacology*; D004347:Drug Interactions; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D009268:Nalidixic Acid / Q000494:pharmacology*; D009675:Novobiocin / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D051381:Rats; D013154:Spleen / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D059005:Topoisomerase II Inhibitors; D014529:Uridine / Q000378:metabolism
D001549:Benzamides; D011838:Radiation-Sensitizing Agents; D059005:Topoisomerase II Inhibitors; D009675:Novobiocin; D009268:Nalidixic Acid; D012313:RNA; C025160:3-aminobenzamide; D004247:DNA; D006690:Bisbenzimidazole; D004229:Dithiothreitol; D013936:Thymidine; D014529:Uridine