Retinoid effects on cell-cell interactions and growth characteristics of normal and carcinogen-treated C3H/1OT1/2...

The effects of retinyl acetate and all-trans-retinoic acid on the growth rate, saturation density, and cytoplasmic underlapping of normal and carcinogen-initiated C3H/1OT1/2 cells were examined. Retinyl acetate (a) decreased the saturation density by as much as 45%, (b) had no effect on the growth rate, (c) reduced cytoplasmic underlapping of adjacent cells by 55 to 85%, and (d) inhibited neoplastic transformation by methylcholanthrene. The effects were dose dependent and not significantly affected by the serum concentrations over the range of 2.5 to 10%. In contrast, all-trans-retinoic acid (a) decreased the saturation density as effectively as retinyl acetate, but only in medium containing 10% serum; (b) significantly reduced the growth rate of cells at low density, especially at low serum concentrations; (c) had no effect upon cytoplasmic underlapping; and (d) enhanced transformation at nontoxic concentrations in medium containing 5% serum but had no effect in 10% serum. We conclude that the effects of retinoids on the growth rate and saturation density of cells in culture may not be relevant to their inhibition of neoplastic transformation. Rather, we interpret the results of our experiments on cytoplasmic underlapping as an indication that retinoids inhibit transformation by stabilizing and/or enhancing cell surface receptors involved in cell-cell contact-dependent formation of a stable monolayer.