The relation between protein accumulation and cell cycle traverse of human NHIK 3025 cells in unbalanced growth

Abstract

Human NHIK 3025 cells, synchronized by mitotic selection, were given 2 mM thymidine, which inhibited DNA synthesis without reducing the rate of protein accumulation. After removal of the thymidine the cells proceeded towards mitosis and cell division, with an S duration 2 hours shorter than, but a G2 and M duration nearly identical to that of the control cells. If cycloheximide (1.25 muM) was present together with thymidine, no net protein accumulation took place during the treatment, and the subsequent duration of S, G2, and M was similar to that of untreated cells. The shortening of S seen after treatment with thymidine alone would therefore indicate that the rate of DNA synthesis depended on the amount of some preaccumulated protein. The postreplicative period in thymidine-treated cells was lengthened by cycloheximide treatment although the protein content had already been doubled. This suggests that proteins required for the traverse of this part of the cell cycle might have to be synthesized after completion of DNA replication. Shortly after removal of thymidine, the rate of protein accumulation declined markedly, indicating the existence of some mechanism for negative control of cell mass. In addition, the daughters of thymidine-treated cells had their cell cycle shortened by 2 hours. As a result, the cells had returned to balanced growth already in the first cell cycle following the induction of unbalanced growth. In conclusion, our experiments suggest that NHIK 3025 cells might require a minimum time in order to traverse the cell cycle, which is independent of cell mass.

Cell cycle model for growth rate and death rate in continuous suspension hybridoma cultures

“…30 The value of t B can be estimated as follows: at maximum growth rate, practically all cells are cycling. Therefore, the noncycling fraction,fo, can be neglected.…”

“…The constant duration of phase B, tB, is approximately equal to the minimum time required for a cell to traverse the entire cycle. 30 The value of t B can be estimated as follows: at maximum growth rate, practically all cells are cycling. Therefore, the noncycling fraction,fo, can be neglected.…”

The role of the G1 period in the life cycle of eukaryotic cells

“…The existence of an irreducible length of G1 period in CHO (Stancel et al, 1981), HeLa, and AKR-MCA cells (present study) after hydroxyurea treatment suggests that certain events during G1 period have to be completed in order for a cell to initiate DNA synthesis. Ronning and Seglen (1982), who studied the effects of synchronization of human NHIK 3025 cells by excess thymidine treatment on the duration of GI phase in the subsequent cycle, came to a similar conclusion.…”

Analysis of cell proliferation in Drosophila wing imaginal discs using mosaic clones

“…Smith and Martin model considered here has sound experimental confirmation (Robinson et al, 1976;Shields, 1978;Shields et al, 1978;Ronning and Seglen, 1982;Rabinovich, 1983) and served as a basis for theoretical models describing the curves of labeled mitoses (Cain and Chau, 1997). We have demonstrated that the model of Smith and Martin is less accurate in describing our experimental data than is our model ascribing the major role in the heterogeneity of proliferation rates to the dispersion of the rates of cell-cycle progression in a deterministic phase.…”