Duration of Bronchial Squamous Metaplasia Produced in Dogs by Cigarette Smoke Condensate2

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Abstract
Cigarette smoke condensate, 0.05 to 0.1 ml, was applied on the left mainstem bronchus of dogs daily, for 8 days, by bronchoscopy. Biopsy 3 days later demonstrated that all animals had developed squamous metaplasia of respiratory mucosa. Two dogs were autopsied at intervals of 3 days, 5, 9, 11, 14, and 18 weeks after the last tar application. Tissue blocks were taken from the trachea down to the lobar bronchi in an unbroken series so that this entire area could be scanned histologically. At 3 days, squamous metaplasia extended from the terminal trachea into the left mainstem bronchus with some spread to the right side. By 5 weeks, the squamous metaplasia had declined as the major abnormality, and a transitional type of epithelium was most prominent. At 9 weeks normal, transitional, and hyperplastic epithelium occurred in equal frequency. Hyperplasia predominated at 11 weeks, though the transitional state persisted in some areas. At 14 weeks, hyperplastic zones occurred at peak frequency alternating with normal epithelium. By 18 weeks essentially all epithelium was normal. These results demonstrate that squamous metaplasia can be induced rapidly in dogs by cigarette smoke condensate. Reversal occurred in a sequence of abnormal epithelial states of differentiation which, though progressively more normal, did not reach normal until several divisions of basal cells were presumed to have occurred. The suggestion is made that abnormal differentiation persisting through several cell generations in the absence of further irritant identifies basal cells as the probable site of action of the tar and indicates that these cells were so altered as to produce daughter cells which failed to differentiate normally.