Isolation and characterization of mouse mutant embryonal carcinoma cells which fail to differentiate in response to retinoic acid.

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Abstract
Murine embryonal carcinoma cells from line PCC4.aza1R differentiate readily in response to retinoic acid. By treating PCCR.aza1R cells with the mutagen N-methyl-N''-nitro-N''-nitrosoguanidine, 2 embryonal carcinoma lines were derived in which the cells failed to differentiate during exposure to retinoic acid. Although these dif(RA)- cells maintained the tumorigenic potential of the parental cells, they differentiated poorly in tumor form. Similarly, the tendency of dif(RA)- cells to differentiate when aggregated in vitro was diminished relative to that of PCC4.aza1R cells. The rate of retinoic acid uptake in cells from the 2 mutant lines did not appear to be reduced compared with the rate in cells from the parental line; specific cytoplasmic retinoic acid-binding protein activity was virtually absent in both mutants. Differentiation of embryonal carcinoma cells in response to retinoic acid apparently requires formation of retinoic acid-cytoplasmic retinoic acid-binding protein complexes.