Effects of retinoids on invasion of organ cultures of chick chorioallantoic membrane by adenovirus transformed cells.

Invasion of chick chorioallantoic membrane (CAM) organ cultures by rat 3Y1 cells transformed by the highly oncogenic human adenovirus type 12 (3Y1/12-10 cells) was inhibited by several retinoids tested. The anti-invasive activity of the retinoids was dependent on retinoid concentration and continuous (4 d) exposure of the CAM. The 50% retinoid dose (dose effective in achieving a response in half of the organ cultures) that inhibited invasion was 0.85 micrograms/ml of retinol palmitate, 0.39 micrograms/ml of retinoic acid, or 0.16 micrograms/ml of retinol acetate. This dose was of the same order of magnitude as that which induced CAM differentiation, and was three- to fourfold less than the dose that caused cytotoxic damage of CAM. In addition, the retinoids inhibited 3Y1/12-10 cell growth by approximately 40% at levels over 10-fold higher than those needed for anti-invasion activity. The findings suggest that the anti-invasive activity of retinoids was at least partly due to direct induction of cell differentiation of the CAM host tissue.