Chromatin decondensed by acetylation shows an elevated radiation response.
V-79 Chinese hamster lung fibroblasts exposed to 5 mM n-sodium butyrate were irradiated with 60Co gamma rays and cell survival was determined by the cell colony assay. In a separate set of experiments the acetylated chromatin obtained from these cells was irradiated and the change of molecular weight of the DNA was evaluated by alkaline sucrose density centrifugation. At a survival level of 10(-2) to 10(-4) cells exposed to butyrate were found to be 1.3-1.4 times more radiosensitive than control cells. Exposure of isolated chromatin to 100 Gy of 60Co gamma irradiation generated 0.9 +/- 0.03 single-strand breaks (ssb) per 10 Gy per 10(8) Da and 2.0 +/- 0.3 ssb/10 Gy/10(8) Da for control and acetylated chromatin, respectively. The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion [Heussen et al., Radiat. Res. 110, 84-94 (1987)]. Packing and accessibility of DNA in chromatin appear to be major factors which influence the radiation sensitivity. The intrinsic radiation sensitivity of chromatin in various packing states is discussed in light of the variation of radiation sensitivity of whole cells in the cell cycle which incorporates repair.
Nackerdien
Z
Z
Department of Radiotherapy, Faculty of Medicine, University of Stellenbosch, Tygerberg, Republic of South Africa.
Michie
J
J
Böhm
L
L
D000107:Acetylation; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D002843:Chromatin / Q000528:radiation effects*; D003037:Cobalt Radioisotopes; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D056572:Histone Deacetylase Inhibitors; D011836:Radiation Tolerance
D002087:Butyrates; D002843:Chromatin; D003037:Cobalt Radioisotopes; D056572:Histone Deacetylase Inhibitors; D020148:Butyric Acid