MODULATION OF GROWTH, DIFFERENTIATION, AND MUCOUS GLYCOPROTEIN-SYNTHESIS BY RETINYL ACETATE IN CLONED CARCINOMA CELL-LINES

  • 1 January 1981
    • journal article
    • research article
    • Vol. 66  (6) , 1165-1174
Abstract
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 (10000WT) [both derived from rat tracheas] was investigated with the use of F344 rats. Growth rate was inhibited .apprx. 25 and 50% in 6.6 .times. 10-6 and 3.3 .times. 10-5 M retinyl acetate, respectively, in both cell lines. Cell line T-8 grew mainly as a monolayer; cell line 1000WT 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 T-8 and 1000WT cells. The granules appeared with and without dense cores in EM. Golgi hypertrophy and increased numbers of microvilli were also evident. After T-8 cells were cultured for 7 days in 6.6 .times. 10-6 or 3.3 .times. 10-5 M retinyl acetate, [3H]glucosamine incorporation increased 133- to 147-fold and [14C]serine incorporation increased 12-fold to 20-fold in the high-MW mucous glycoprotein fraction (peak A) from the cell cytosol. In 1000WT cells, [3H]glucosamine incorporation increased 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; 1000WT cells showed a comparatively small but significant increase. [Retinoids are antineoplastic agents.].