Bronchial micronuclei as a marker of an early stage of carcinogenesis in the human tracheobronchial epithelium.

In the bronchial epithelium, smoking initiates a multistep process that first appears histologically as premalignant squamous metaplasia/dysplasia, a biological predecessor of squamous-cell lung cancer. Reflecting chromosomal damage from a carcinogenic insult, micronuclei may reveal earlier events in the carcinogenic sequence. We prospectively evaluated and correlated micronucleus count, histology (index of metaplasia) and smoking exposure in 35 consecutive subjects (9 active smokers, 10 previous smokers and 16 never-smokers) undergoing diagnostic bronchoscopy. Samples for micronuclei and histological evaluation were taken from the main carinal mucosa in each subject for site-specific comparisons. The median and mean micronucleus counts per 1,000 cells were significantly higher in active smokers than in non-smokers (subjects who had never smoked and previous smokers): median counts were 3.7 vs. 1.4, p = 0.03; mean counts were 4.7 vs. 1.9, p = 0.01. There was no significant difference, however, in micronucleus counts between subjects who had never smoked and previous smokers. Bronchial metaplasia and smoking history were not associated. Our findings suggest that micronuclei are a readily quantitated, early intermediate-endpoint marker for detecting tobacco-initiated tracheobronchial carcinogenesis.