Modulation of growth, differentiation, and mucous glycoprotein synthesis by retinyl acetate in cloned carcinoma cell lines.

The ability of retinyl acetate to alter growth, differentiation, and synthesis of mucous glycoproteins in cell lines cloned from an adenocarcinoma (T-8) and a squamous cell carcinoma (1000 WT) was investigated with the use of F344 rats. Growth rate was inhibited approximately 25 and 50% in 6.6 x 10(-6) and 3.3 x 10(-5) M retinyl acetate, respectively. In both cell lines. Cell line T-8 grew mainly as a monolayer, whereas cell line 1000 WT grew as a stratified epithelium. In the presence of both concentrations of retinyl acetate, this stratification was decreased and cells became enlarged and more cuboidal. Retinyl acetate induced the formation of numerous vacuoles and periodic acid-silver methenamine-positive granules in both T-8 and 1000 WT cells. The granules appeared with and without dense cores in electron micrographs. Golgi hypertrophy and increased numbers of microvilli were also evident. After T-8 cells were cultured for 7 days in 6.6 x 10(-6) or 3.3 x 10(-5) M retinyl acetate, [3H]glucosamine incorporation increased 133- to 147-fold and [14C]serine incorporation increased twelvefold to twentyfold in the high-molecular-weight mucous glycoprotein fraction (peak A) from the cell cytosol. In 1000 WT cells, [3H]glucosamine incorporation creased only 4.2- to 7.5-fold, and [14C]serine incorporation increased only 2.6- to 4.6-fold under the same culture conditions. A similar difference in the amount of stimulation was seen for peak A isolated from the secretions. Thus T-8 cells showed a marked increase in the synthesis and secretion of mucins, whereas 1000 WT cells showed a comparatively small but significant increase.