Potentiation by ethanol consumption of tracheal squamous metaplasia caused by vitamin A deficiency in rats

The effect of ethanol (CAS: 64-17-5) consumption on the development of squamous metaplasia of the trachea caused by vitamin A deficiency was assessed in rats. To that effect, weanling male Sprague-Dawley rats were fed for 8-12 weeks either a nutritionally adequate liquid diet containing a standard amount of vitamin A or a diet lacking vitamin A. Littermates were pair-fed the same diets with ethanol (36% of total calories) iso-calorically replacing part of the carbohydrates. In rats fed the vitamin A-deficient diets with or without ethanol, plasma vitamin A was very low (5.3±0.9 and 5.9±1.5 μg/dl; n=20 pairs), while liver and tracheal vitamin A was unmeasurable. Squamous metaplasia was noted in 9 of 20 rats fed the vitamin A-deficient diet and in 13 of 20 rats fed the same diet plus ethanol. Severe lesions (those showing keratinization) were present in 42% of the tracheal sections from rats fed the vitamin A-deficient diet plus ethanol compared to 6% of the sections from rats fed the diet without ethanol (P<.001). In the ethanol-fed group, 37% of all the sections showed metaplasia occupying more than 50% of the tracheal epithelium, whereas in the absence of ethanol, 14% of the sections had lesions occupying more than 50% of the epithelium (P<.001). When the histologic grade and extent of the lesions were expressed as the percentage of rats affected, the differences between the 2 groups of animals were not statistically significant. Ethanol feeding resulted in a 70% increase in the labeling index of basal cells in squamous metaplasia (30.7±3.5 vs. 17.3±1.5%; P<.02). The number of [³H]thymidine-labeled suprabasal cells was not altered after ethanol feeding. In ciliated cells of the tracheal epithelium that were not as yet involved in the formation of metaplasia, ciliary abnormalities and an increased number of lysosomes were observed in rats that had consumed ethanol. In rats fed the regular vitamin A-containing diets with or without ethanol, plasma vitamin A was normal (55.7±2.1 and 47.2±1.7 μg/dl; n=19 pairs). In rats fed ethanol, liver vitamin A levels were significantly decreased (twofold to threefold), but tracheal vitamin A was increased (two-fold) and the basic feature of the pseudostratified ciliated columnar epithelium of the trachea was maintained: No squamous metaplasia was observed in any of these animals. The results of this study indicate that ethanol consumption potentiates the development of squamous metaplasia caused by vitamin A deficiency.