Retinol inhibition of ornithine decarboxylase induction and G1 progression in Chinese hamster ovary cells.

sequential events of the growth response under controlled conditions without the influence of a transforming or promoting stimulus. We have previously demonstrated in mitotically syn chronized CHO4cells that vitamin A treatment arrested cells in mid-G1 phase (16, 17). The inhibitory effect of vitamin A was a function of cell cycle position; cell cycle progression was blocked only when retinol was added to the cells prior to mid G1 progression. The arrest was reversible and resulted in a 2hr delay in the onset of DNA synthesis in cells exposed to a G1 pulse of retinol, suggesting that, in the presence of the vitamin, the cells progressed to a point in mid-G1 prior to some key event required for G1-S-phase transition. An increase in ODC activity is a ubiquitouseventmarkingG1progressionof prolif erating cells (28, 57). The excursion of ODC activity in retinol treated cells was used, therefore, as a marker of the extent of G1 progression to localize the temporal site of vitamin action. It was found that the vitamin-induced arrest blocked the cells at a site prior to the induction of ODC. These results suggested the presence of a retinol-sensitive restriction (50) or commit ment point in CHO cells during mid-G1 phase and that ODC induction was associated with passage through or beyond this point. In the present studies, we have examined this relation ship between the inhibition of ODC and the inhibition of growth in order to establish any obligatory correlations between the 2 vitamin-inhibited processes.