Inhibition of transformation of primary rat tracheal epithelial cells by retinoic acid.

The effect of retinoic acid (RA) on N-methyl-N'-nitro-N-nitrosoguanidine-induced transformation of primary cultures of rat tracheal epithelial cells was investigated. RA inhibited transformation of rat tracheal epithelial cells by up to 95% at concentrations of 3.3 to 33 nM which did not substantially affect cell survival. The inhibitory effect of RA on transformation was concentration dependent and was also dependent upon timing and duration of treatment. Treatment with RA for only 1 week following N-methyl-N'-nitro-N-nitrosoguanidine exposure diminished the transformation frequency by 30 to 57%, although longer treatment times were more effective. Because RA was able to inhibit transformation effectively at concentrations which were not substantially inhibitory to colony-forming efficiency of rat tracheal epithelial cells, the mechanism of inhibition of cell transformation does not seem to be related to cytotoxic effects of RA known to occur at high RA concentrations.