Rapaport E, Schroder E W, Black P H
J Cell Physiol. 1982 Mar;110(3):318-22. doi: 10.1002/jcp.1041100317.
Exposure of Swiss 3T3 cells to micromolar quantities of beta-all-trans-retinoic acid (RA) results in either inhibition of growth or stimulation of cellular responsiveness to mitogens, depending on the length of treatment. Inhibition of growth is produced by treatment of the cells with RA for at least 48 hours. The total cellular pools of adenosine 5'-triphosphate (ATP) are markedly increased after 48-hour RA treatment and dose dependence studies show a correlation between the expanded ATP pools and the inhibitor effects. The expansion of total cellular ATP pools by retinoic acid occurs throughout the cell cycle and parallels the cell cycle-dependent fluctuations in total cellular ATP pools of untreated cells. Studies of [3H]thymidine incorporation and labeling indices in intact cells and [3H]dTTP incorporation and labeling indices in isolated nuclei of RA-treated and control cultures suggest that cellular acid-soluble nucleotide pools mediate the inhibition of DNA replication in the 48-hour-RA-treated cells. The stimulatory activity of RA for mitogenic responsiveness is demonstrated by treatment of G0/G1-arrested 3T3 cells with micromolar levels of RA for a maximum of 18 hours resulting in the potentiation of phorbol myristate acetate (PMA)-stimulated transition into S phase of the cell cycle. Marked increases in total cellular ATP and UTP pools are produced by 18-hour treatment of G0/G1-arrested cells with RA, before their exposure to PMA.
将瑞士3T3细胞暴露于微摩尔量的全反式维甲酸(RA)中,根据处理时间的长短,会导致生长抑制或细胞对有丝分裂原反应性的刺激。用RA处理细胞至少48小时会产生生长抑制。48小时的RA处理后,细胞内三磷酸腺苷(ATP)的总池显著增加,剂量依赖性研究表明扩大的ATP池与抑制作用之间存在相关性。视黄酸引起的细胞内总ATP池的扩大在整个细胞周期中都会发生,并且与未处理细胞的细胞内总ATP池的细胞周期依赖性波动平行。对完整细胞中[3H]胸腺嘧啶核苷掺入和标记指数以及RA处理和对照培养物的分离细胞核中[3H]dTTP掺入和标记指数的研究表明,细胞酸溶性核苷酸池介导了48小时RA处理细胞中DNA复制的抑制。RA对有丝分裂反应性的刺激活性通过用微摩尔水平的RA处理G0/G1期停滞的3T3细胞最多18小时来证明,这导致佛波酯肉豆蔻酸酯(PMA)刺激的细胞周期向S期转变的增强。在用RA处理G0/G1期停滞的细胞18小时后,在它们暴露于PMA之前,细胞内总ATP和UTP池显著增加。