Showing papers by "Michael B. Sporn published in 1974"

α and β-Retinyl acetate reverse metaplasias of vitamin A deficiency in hamster trachea in organ culture

Abstract: DEFICIENCY of vitamin A causes a well-defined lesion, namely keratinised squamous metaplasia, in tracheobronchial epithelium1. In this lesion, the normal columnar ciliated and mucus cells of the epithelium, which depend on vitamin A for their formation, are totally replaced by squamous cells which produce keratin. The mechanism of action of vitamin A in controlling this normal differentiation of ciliated and mucus cells is still unknown. We report here an in vitro system for studying this process, using organ culture of hamster tracheas in a chemically defined, serum-free medium. Growth of tracheas in this medium without vitamin A causes keratinised squamous lesions. Addition of vitamin A to the organ cultures after development of such lesions causes reversal of the process of keratinisation and replacement of the squamous cells by columnar ciliated and mucus cells.

Vitamin A deficiency enhances binding of benzo(a)pyrene to tracheal epithelial DNA

Abstract: THE relationship between carcinogen action and the state of cellular differentiation in target tissues is still unclear. Vitamin A controls the state of differentiation in many epithelial tissues1, including those of the respiratory tract2,3. Vitamin A can also modify the process of carcinogenesis in many tissues; in a variety of experiments, the results obtained have often been influenced by experimental variables such as the animal species, the time and route of vitamin A administration, and the morphological type and the tissue site of tumour induced4–10. In the respiratory epithelium2 vitamin A deficiency causes basal cell hyperplasia and squamous metaplasia. In order to study the possible relationship of the altered state of differentiation of respiratory epithelium to chemical carcinogenesis in this tissue, we have studied the binding of tritiated benzo(a)pyrene (3H-BP) to DNA in tracheal epithelial cells of normal and vitamin A deficient hamsters. The binding of carcinogens to DNA has been indicated as a potentially crucial step in the carcinogenic process11–13. For polynuclear hydrocarbons such as benzo(a)pyrene, this binding is presumed to be the ultimate result of metabolism to reactive carcinogenic forms14–16; the extent of binding may be a measure of the carcinogenic potential towards a given tissue.

The Reversal of Keratinized Squamous Metaplastic Lesions of Vitamin A Deficiency in Tracheobronchial Epithelium by Vitamin A and Vitamin A Analogs in Organ Culture: A Model System for Anti-Carcinogenesis Studies

Abstract: Normal cellular differentiation in tracheobronchial epithelium is dependent on vitamin A. In the absence of vitamin A the normal ciliated and mucus-producing cells of this epithelium are replaced by squamous cells, which are neither ciliated nor mucus-producing, but which do produce keratin. We have developed an in vitro system for studying the above process, using organ culture of hamster tracheas in chemically defined, serum-free medium. Keratinized squamous lesions of tracheobronchial epithelium can be induced by absence of vitamin A in the defined medium. Addition of vitamin A or its analogs to the culture (after such lesions have formed) induces reversal of keratinization and growth of a new ciliated and mucus-producing epithelium. A single one-day dose of all-trans-retinyl acetate or all-trans -retinoic acid is sufficient to effect reversal of keratinization. The hamster tracheobronchial organ culture system is also being used in our laboratory to determine whether vitamin A and its analogs are capable of reversing squamous metaplastic or other preneoplastic lesions that are induced by chemical carcinogens.