INFLUENCE OF HISTONE ACETYLATION ON THE MODIFICATION OF CYTOPLASMIC AND NUCLEAR PROTEINS BY ADP-RIBOSYLATION IN RESPONSE TO FREE-RADICALS

Inhibition of histone deacetylase by addition of 5 mM n-sodium butyrat e to the growth medium increases the utilization of [P-32]NAD(+) and A DP-ribosylation (ADPR) of total cellular proteins of V79, HeLa, mouse B16, mouse Fib/T and human T1 kidney cells by a factor of 1.2-2.3. Whe n the ADP-ribosylase is challenged by exposing cells to damage by . OH radicals (25 mu M CuSO4 2.8 mM H2O2) ADPR increases by factors of 5.7 -6.0 and 3.2-4.0 in normal and butyrated cells, respectively. Operatio n of the free radical generator is supported by the response to EDTA a nd radical scavengers. Densitometric analysis of autoradiographs from SDS-gels show that butyrate exposure increases basal ADPR-modification of histones from T1 cells by factors of 1.1-1.9. Addition of . OH rad icals increases the ADPR modifications of histones 4.4-8.7-fold in nor mal cells and 3.2-6.7-fold in butyrate exposed cells. Butyrate exposur e elevates base level ADPR-modification and seduces subsequent ADPR-mo dification initiated by DNA damage. The results are consistent with th e view that ADPR-modification and histone acetylation have overlapping functions and probably induce similar structural changes in chromatin .