Reversal of the promotional effect of 12-O-tetradecanoylphorbol-13-acetate on morphological transformation of hamster embryo cells by glucocorticoids.

The effects of glucocorticoids and cholesterol on morphological transformation have been studied using hamster embryo cells. The cells were exposed sequentially to benzo[a]pyrene (BP) (3 days) and the tumor promotor 12-O-tetradecanoylphorbol-13-acetate (TPA) (4 days) before scoring for morphologically transformed colonies. Dexamethasone and hydrocortisone strongly inhibited the formation of morphologically transformed colonies when applied to the cells in the second period of exposure together with TPA, but had no effect when present with BP during the first period. Corticosterone had only a weak effect, while cortisone had no effect on the transformation frequency. Cholesterol gave rise to an enhanced number of transformed colonies. Dexamethasone, being the most potent compound tested, inhibited morphological transformation by more than 50% when present in a concentration of 0.25 nM. The finding that dexamethasone reduced the frequency of transformation even when added only 6 h prior to staining, indicates that the glucocorticoids may also reduce the transformation frequency by reversing morphologically transformed cell colonies to a normal appearance.