Effects of retinoic acid on the transformation and metabolic cooperation of rat liver cells in vitro, and on the growth of hepatoma cells in vivo

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Abstract
By different experimental approaches in culture, we obtained convergent responses to 13 cis-retinoic acid (RA) in rat liver epithelial cell lines. We showed that the degree of transformation of the cells which had already been spontaneously transformed in culture, could be enhanced, since the capacity of these cells both to grow in soft agar and to express .gamma.-glutamyl transpeptidase increased markedly. We also showed that RA acted synergistically with a promoter, 12-tetradecanoyl-phorbol-13-acetate (TPA), as regards the promoter''s property of blocking the metabolic cooperation between cells. RA did not, however, trigger cell transformation in the lines which had not yet been transformed, and unlike TPA, did not by itself inhibit intercellular communications. On the other hand, in our in vivo experiments, it appeared that RA, by slowing down the growth of a transplanted rat hepatoma, might have a slightly protective effect against tumor development.