 cell culture systems are instrumental in elucidating regulation of normal function and mechanisms of its perturbation by toxic substances . to this end 
 , three applications of epithelial cells cultured with 3t3 feeder layer support are described . 
 first , treatment of the premalignant human epidermal keratinocyte line scc-12f2 with the tumor promoter 12-o - tetradecanoylphorbol-13-acetate suppressed cell growth and differentiation . 
 this agent produced a biphasic growth response greatly inhibiting cell growth at 1 to 10 nm , but much less above 100 nm . 
 expression of the differentiated functions involucrin and transglutaminase was found to be inhibited markedly at concentrations above 10 nm . 
 second , 3-methylcholanthrene toxicity was surveyed in a variety of rat epithelial cell types . 
 the two most sensitive to growth inhibition were epidermal and mammary epithelial cells , while those from bladder , prostate , thyroid , and endometrium were insensitive to growth inhibition . 
 great differences were evident even among those cells derived from stratified squamous epithelia ( epidermal , esophageal , vaginal , forestomach ) despite their expression of aryl hydrocarbon hydroxylase activities to similar degrees . finally , 
 expression of estrogen receptors in rat endometrial cells was shown to be stimulated by the camp - elevating agent forskolin . 
 maximal stimulation of 3- to 6-fold occurred in 6 hr , compatible with a requirement for protein synthesis . 
 although expressing keratinocyte character ( transglutaminase activity and envelope forming ability ) , the cells thus retain some hormonal character that may be modulated by camp - dependent kinase activity . 
 pursuit of such results will aid in understanding differences in response among cell types and species , in elucidating mechanisms of action of known toxic substances and , ultimately , in predicting toxicity of less well understood agents.imagesfigure 1.figure 4 . 
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