Effect of n-butyrate on cell cycle progression and in situ chromatin structure of L1210 cells☆

摘要: Abstract In the presence of 1–5 mM n -butyrate, murine leukemic L1210 cells cease proliferation and become arrested in G1A compartment G1 phase. Cells this compartment, comparison with remaining phase (G1B), are characterized by low RNA content more condensed chromatin. During unperturbed growth cell residence times indeterminate duration (exponentially distributed); half-time is about 1.4 h. The effect -butyrate arresting was concentration-dependent. However, sensitivity to drug markedly enhanced when were treated for longer than one generation (12 h). remained viable removed, after a lag period, they resumed progression through cycle. on various parts cycle studied stathmokinetic experiment. rate entrance into mitosis decreased 30, 60 110%, 1, 2.5 5 respectively, thus indicating slowdown G2 S. prolonged 20, 70 140% at respectively. increased as much 1.5-, 6.3- 15.6-fold -butyrate. Progression late (G1B) not affected 1 mM, could be estimated higher concentrations. effects evident h addition DNA situ nuclei -butyrate-treated had lowered (by 2–8 °C) stability thermal denaturation 15%) accessibility DNase I. decrease heat pronounced permealized heated MgCl 2 rather EDTA. also showed acid-induced denaturation. Changes chromatin seen all cells, regardless phase, within first hours Mitotic however, reacted rapidly interphase cells. observed changes most likely consequence histone modifications (acetylation inner histones, dephosphorylation H1) induced