Ethanol potentiates squamous metaplasia of the rat trachea caused by vitamin A deficiency

The effect of ethanol consumption on the development of squamous metaplasia of the trachea caused by vitamin A deficiency was studied in rats fed for 8-14 weeks with either normal vitamin A-containing diets or diets lacking vitamin A. Littermates were pair-fed the same diets with carbohydrates (36% of energy) replaced by ethanol. In rats fed the normal vitamin A diet with or without ethanol the tracheal mucosa was lined by a pseudostratified ciliated columnar epithelium; no squamous metaplasia was observed. Serum vitamin A was normal in both groups. Squamous metaplasia was noted in 4 of 7 rats fed the vitamin A-free diet and in 6 of 7 animals fed the vitamin A-free diet plus ethanol; the lesions were present in 48 and 68% of all the sections, respectively. Furthermore, the most severe lesions were seen only in the vitamin A-free diet plus ethanol group. Serum vitamin A was low in both groups. Ethanol consumption also results in lysosomal and ciliary abnormalities in the ciliated cells of the tracheal epithelia that were not as yet involved in the formation of squamous metaplasia. Thus, these synergistic effects of vitamin A deficiency and ethanol could contribute to the enhanced incidence of respiratory cancer seen in the alcoholic.