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.