Dynamics of smoking-induced mutagenesis in normal epithelium

Smoking leads to carcinogen-induced mutagenesis in lung tissue, increasing the risk of acquisition of cancer-driving mutations. Epidemiological studies have suggested that quitting smoking has a cumulative beneficial effect. In this study, Peter Campbell and colleagues examine the mutational status of 632 single-cell colonies from normal bronchial epithelium from smokers, ex-smokers and individuals who have never smoked. The findings suggest that smoking increases genomic heterogeneity, with episodic contributions of known and novel mutational signatures. Whereas cells from current smokers show an enrichment in mutated cancer drivers, cells from ex-smokers have a near-normal mutational burden and longer telomeres, which suggests that the benefit of smoking cessation is linked to replenishment of the bronchial epithelium with near-normal cells.