Hydrocortisone modulates RA-induced growth inhibition of normal and transformed human embryonic lung fibroblasts

All-trans retinoic acid (10(-5) M) added at seeding reduces the growth rate and saturation density of normal human embryonic lung fibroblasts of two lines (WI-38 and IMR-90) and similarly inhibits growth of SV40-transformed WI-38 cells (VA13A). The growth inhibitory effects of retinoic acid do not show serum dependency, and the viability of treated cells is 95-99% of controls. Old populations of WI-38 cells (cells at high population doubling levels) are more sensitive to the effects of retinoic acid than are young populations (cells at low population doubling levels), and population life span is reduced by continuous exposure to retinoic acid. When retinoic acid is combined with the glucocorticoid hydrocortisone, inhibition of VA13A cell growth is increased, whereas the retinoic acid-induced inhibition of normal cells is decreased. VA13A cells treated with retinoic acid alone, or in combination with hydrocortisone, exhibit a reversion to a more elongated, fibroblast-like appearance. This paper discusses the clinical implications of the relationship between retinoic acid and hydrocortisone.