Prevention and reversal by a retinoid of 3,4-benzpyrene- and cigarette smoke condensate-induced hyperplasia and metaplasia of rodent respiratory epithelia in organ culture.

The influence of an aromatic analog of vitamin A, etretinate, on the effects of 3,4-benzpyrene and cigarette smoke condensate has been investigated in fetal mouse lung and neonatal rat tracheas grown in organ culture. In both tissues, 3,4-benzpyrene as well as cigarette smoke condensate induces a striking increase of epithelial mitosis within 12--14 days of treatment. The increase is associated with a loss of secretory activity and of ciliary function. These changes persist in the absence of benzpyrene or smoke condensate in explants transferred to control medium. Treatment with etretinate alone does not affect the normal epithelial growth rate or normal differentiation. If combined with either benzpyrene or smoke condensate, the aromatic compound inhibits the increase in cell division and prevents the loss of secretory activity or ciliary function. In explants pretreated with 3,4-benzpyrene or cigarette smoke condensate, etretinate reduces the carcinogen- or smoke condensate-induced increase in mitotic activity to normal levels and restores secretory differentiation and ciliary function. The mechanism of action involved in the anticarcinogenic activity of the retinoid is discussed.