Retinyl acetate modulation of cell growth kinetics and carcinogen--cellular interaction in mouse epidermal cell...

Exposure of mouse epidermal cell cultures to beta-retinyl acetate (RA) affects a number of parameters presumed to be important in chemical carcinogenesis. (1) RA alters the course of differentiation of the epidermal cells in culture resulting in a reduced rate of cell death which normally follows cellular maturation during the first two weeks in culture. The extended life span of the cultures appeared due to prolonged survival of cells and not to increased growth rate since RA inhibited the rate of cellular proliferation. This inhibition took place only after completion of a full cell cycle in the presence of RA. (2) DNA repair in response to physical and chemical agents was quantitatively unaffected in the presence of RA. (3) The activity of constitutive aryl hydrocarbon hydroxylase (AHH) was slightly decreased after exposure to RA but the level of enzyme induced by benz[a]anthracene was strongly reduced to 20% of the controls. (4) In the presence of RA, binding of 7,12-dimethylbenz[a]anthracene to epidermal cell DNA was markedly decreased. In contrast, binding to cellular protein was significantly increased by the retinoid.