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 tract^2,3. 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 induced^4–10. 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 process^11–13. For polynuclear hydrocarbons such as benzo(a)pyrene, this binding is presumed to be the ultimate result of metabolism to reactive carcinogenic forms^14–16; the extent of binding may be a measure of the carcinogenic potential towards a given tissue.