Kaminskas E, Field M, Henshaw E C
Biochim Biophys Acta. 1976 Sep 24;444(2):539-53. doi: 10.1016/0304-4165(76)90398-6.
Cyclic AMP levels in Ehrlich ascites tumor cells changed little after deprivation of cells of essential nutrients, serum, glucose and amino acids, deprival of each of which leads to marked inhibition of growth and protein synthesis. Cyclic AMP levels also changed little after the addition of these nutrients to deprived cells. Thus cyclic AMP is not likely to be the intracellular mediator for growth regulation by these three nutrients. Elevation of cyclic AMP levels for short periods by exposure of cells to choleratoxin or theophylline produced only slight changes in parameters of protein synthesis (polyribosome pattern and rate of [3H]leucine incorporation). An exposure for 1 day to dibutyryl cyclic AMP did not inhibit cell growth. However, prolonged exposure to dibutyryl cyclic AMP inhibited the multiplication of Ehrlich ascites cells both in suspension and in stationary cultures. No morphological effects were evident in the former; in the latter, cells attached firmly to the substratum and formed elongated cytoplasmic processes. Inhibition of cell multiplication by dibutyryl cyclic AMP was related to cell density and to serum concentration. Cells in dibutyryl cyclic AMP-containing media plated at low cell densities multiplied as rapidly as control cells. The final densities cells reached were determined by the serum concentration; in dibutyryl cyclic AMP-containing media these densities were about one-half those of respective control cells. Limitation of cell multiplication by dibutyryl cyclic AMP was reversed by the addition of serum, by resuspending cells at lower densities, or by resuspending cells in media without dibutyryl cyclic AMP. These findings suggested that dibutyryl cyclic AMP may affect the utilization of serum factors by cells. Dibutyryl cyclic AMP did not inactivate serum factors and did not change the rate at which cells depleted the growth medium of serum factors. Dibutyryl cyclic AMP may limit cell multiplication by increasing the cellular requirement for serum factors.
艾氏腹水癌细胞在缺乏必需营养素、血清、葡萄糖和氨基酸后，环磷酸腺苷（cAMP）水平变化不大，而缺乏其中任何一种都会导致生长和蛋白质合成受到显著抑制。将这些营养素添加到缺乏营养素的细胞中后，cAMP水平变化也不大。因此，cAMP不太可能是这三种营养素调节生长的细胞内介质。通过将细胞暴露于霍乱毒素或茶碱使cAMP水平短期升高，仅使蛋白质合成参数（多核糖体模式和[3H]亮氨酸掺入率）发生轻微变化。暴露于二丁酰环磷酸腺苷（dbcAMP）1天并不抑制细胞生长。然而，长期暴露于dbcAMP会抑制悬浮培养和静止培养的艾氏腹水细胞的增殖。在前者中没有明显的形态学影响；在后者中，细胞牢固地附着于基质并形成伸长的细胞质突起。dbcAMP对细胞增殖的抑制与细胞密度和血清浓度有关。以低细胞密度接种在含dbcAMP培养基中的细胞增殖速度与对照细胞一样快。细胞最终达到的密度由血清浓度决定；在含dbcAMP的培养基中，这些密度约为各自对照细胞的一半。添加血清、以较低密度重悬细胞或在不含dbcAMP的培养基中重悬细胞可逆转dbcAMP对细胞增殖的限制。这些发现表明，dbcAMP可能会影响细胞对血清因子的利用。dbcAMP不会使血清因子失活，也不会改变细胞耗尽血清因子生长培养基的速度。dbcAMP可能通过增加细胞对血清因子的需求来限制细胞增殖。
