Response of laryngeal and tracheo-bronchial surface lining to inhaled cigarette smoke in normal and vitamin A-deficient rats: a scanning electron microscopic study.

The effects on surface morphology of airway epithelium of cigarette smoke (CS) inhalation alone (experiments one and two) or of CS in combination with hypovitaminosis A (experiment two) was investigated using specific pathogen free rats. Eight morphologically distinct cell types were distinguished overall. Apart from atypical squamous lesions, each of the other cell types could be found in varying proportions in all experimental groups. CS alone caused an increase in the frequency with which intra-lumenal mucus was seen and an increase in the occurrence of secretory cells of types IV (i.e., 'merocrine') and V (i.e., 'apocrine'). In experiment one, the area of trachea covered by cilia as determined by point counting increased significantly (P less than 0.01). Hypovitaminosis A was induced by lowering the dietary intake of vitamin A to a minimum, defined level. Rats showed an approximately 75% decrease in plasma retinol levels and a 95-100% decrease in hepatic stores of vitamin A. At this level, hypovitaminosis A alone had no significant effect on airway epithelial morphology. Foci of squamous metaplasia (squamous cells of type VIIIa) were found in all groups but extensive squamous metaplasia of the larynx and squamous lesions of atypical appearance (type VIIIb) were found only in the vitamin deficient group exposed to CS. The results suggest the synergistic effects of reduced vitamin A and CS may be important in the induction of atypical squamous changes which may predispose the airway to the development of squamous carcinoma.