Formation of proliferative tetraploid cells after treatment of diploid cells with sodium butyrate in rat 3Y1 fibroblasts

Abstract

When randomly proliferating rat 3Y1 fibroblasts were treated with sodium butyrate, more than 90% of their cells were arrested reversibly with a 2C DNA content at least 12 h before the G1/S boundary. When cells synchronized in the early S phase were treated with butyrate, approximately 70% of all cells were arrested with a 4C DNA content. The arrests in both G1 and G2 phases by the single inhibitor suggest that the two phases share a common mechanism. The ability of cells to undergo mitosis on time was quickly lost with time of arrest in the G2 phase. Upon removal of the inhibitor, the cells arrested with a 4C DNA content entered a new S phase without intervening mitosis. The tetraploid cells thus produced kept proliferating as fast as diploid cells. These results suggest that the inhibition of the normal G2 traverse is somehow responsible for the formation of the proliferative polyploid cells.

The SIN3/RPD3 Deacetylase Complex Is Essential for G2 Phase Cell Cycle Progression and Regulation of SMRTER Corepressor Levels

“…While the cell cycle distribution of RPD3 RNAi cells was similar to that of control cells, the reduced growth rate of these cells suggests a delay at multiple points in the cell cycle, presumably including both the G 1 and G 2 /M phases. Chemical inhibitors of deacetylases cause both G 1 and G 2 phase arrests, supporting a role for RPD3 at these points in the cell cycle (14,30,74,75). Taken together, the growth rate and cell cycle distribution data indicate that SIN3, RPD3, and p55 play regulatory roles during the cell cycle but SAP18 and SAP30 do not.…”

“…Yeast RPD3-null mutants exhibit a global increase in acetylation at lysine 5 (K5) and K12 of histone H4 and K9/18 and K14 of histone H3 (54). Furthermore, treatment of mammalian tissue culture cells with HDAC inhibitors, including sodium butyrate, trichostatin A, and trapoxin, leads to a global increase in histone acetylation levels and arrest in the G 1 and G 2 phases of the cell cycle (14,30,31,36,45,49,52,58,74,75,76).…”

“…Loss of certain HATs that preferentially acetylate histones H3 or H4 or mutation or deletion of conserved lysine residues in the N-terminal tail of histone H4 leads to arrest in the G 2 /M phase (22,41,42,71,79). Similarly, chemical inhibitors of HDACs have been reported to have antiproliferative effects on mammalian cells, including arrest of the cell cycle in the G 1 and/or G 2 phases (14,30,31,36,45,49,52,58,74,75,76). These observations highlight the importance of the balance of histone acetylationdeacetylation during the cell cycle.…”

Polyploidization of Murine Mesenchymal Cells Is Associated with Suppression of the Long Noncoding RNA H19 and Reduced Tumorigenicity

“…Tetraploidization was conducted as previously reported (31). Briefly, cells were treated with 1 mmol/L hydroxyurea (Sigma) followed by 5 mmol/L sodium butyrate (Sigma).…”

Butyrate Enhances the In Vitro Anti-SRBC (Sheep Red Blood Cell) Antibody Responses in Murine Splenocytes

“…When butyrate at millimolar concentrations is added to the culture of cell lines, it inhibits the proliferation, arrest ing the cell cycle predominantly in the G1 phase and some times in the G2 phase (2)(3)(4)(5). It also induces a differentia tion in human and murine tumor cell lines; that is, in crease of membraneous antigens and enzymatic activities (6)(7)(8)(9)(10).…”