Virchows Arch. B Cell Path. 33, 199-212(1980) 9 by Springer-Verlag 1980 Original Articles Ultrastructural Analysis of the Retinoid-Induced Reversal of Epithelial Hyperplasia and Metaplasia Alex Matter 1, Laur6e Mfiller-Salamin 1, Ilse Lasnitzki2, and Werner Bollag 1 Pharmaceutical Research Division, F. Hoffmann-LaRoche & Co. Ltd., Basle, Switzerland 2 StrangewaysResearch Laboratory, Cambridge, England Summary. The 7,12-dimethylbenzanthracene-induced skin papilloma of the mouse and the 3-methylcholanthrene-induced hyperplasia and metaplasia in prostate organ cultures were studied by electron microscopy. The two types of tissue both showed a reversal of hyperplasia and metaplasia when treated with retinoids (= vitamin A and analogs). This reversal was reached by means that are quite characteristic for a given type of tissue. In the skin, DNA-synthetic activity was not influenced by retinoid treatment. There was, however, considerable necrosis and an impressive mucous metaplasia. The latter might be at least partly responsible for the cell loss, probably through a loss of anchorage in the prickle-cell layer. In the prostate, no mucous metaplasia was observed, but there was an important depression of DNA-synthetic activity. The secretory apparatus reappeared together with the microvilli, possibly induced by the slowing down of cell division. Key words: Retinoids - Vitamin A - Carcinogenesis - Ultrastructural analy- sis. Introduction Vitamin A is important for physiological functions such as growth, vision and fertility and for the differentiation of epithelial tissues. In vitamin A deficiency, the epithelia of the respiratory tract and of accessory sex organs such as the prostate gland undergo squamous metaplasia (Wolbach and Howe, 1925 ; Wong and Buck, 1971) while excess vitamin A induces a mucous metaplasia of squa- mous epithelia (Lasnitzki, 1963; Wong, 1975). Possibly linked to this latter function, vitamin A and its analogs (retinoids) have been shown to prevent and reverse hyper- and metaplastic changes in vitro (Chopra and Wilkoff, 1976; Lasnitzki, 1974; Sporn et al., 1975) and even to inhibit the induction of tumors by carcinogens in vivo (Bollag, 1971a; 1971b; 1972; 1974; 1975a; 1975b; Chu and Malmgren, 1965; Davies, 1967; Rowe and Gorlin, 1959; Saffiotti et al., Of]print requests to: A. Matter 0340-6075/80/0033/0199/$02.80