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Genetics: Signals of smoking diminished in ex-smokers

Nature

January 30, 2020

A subset of cells from the lungs of ex-smokers have been shown to have similar levels of mutations to those found in cells from non-smokers, reports a paper published online this week in Nature. The study, involving cells from 16 individuals, suggests that quitting smoking may result in the partial replenishment of lung tissue by cells that have not been damaged by tobacco exposure.

To understand the effects of smoking at the cellular level, Peter Campbell and colleagues studied bronchial epithelial cells from 16 people: 3 children, 4 never-smokers, 6 ex-smokers and 3 current smokers. They generated 632 colonies derived from single bronchial cells and sequenced their genomes to obtain a dataset of genetic mutations. The authors found that smoking resulted in the most mutations, but, unexpectedly, it also resulted in increased variability in the number of mutations (mutational burden) from cell to cell within the same individual. Cells from the same biopsy of bronchial epithelium could vary by 10 times in the number of mutations (from 1,000 per cell to over 10,000 per cell).

Although most of the cells from ex- or current smokers had increased levels of mutations, the authors also identified some cells that showed similar levels of mutation to those found in never-smokers of the same age. Cells with a near-normal mutational burden were rarely present in the current smokers, but they were four times more frequent in ex-smokers, accounting for 20 - 40% of the cells studied. The authors found that the cells with a near-normal mutational burden had longer telomeres than did their more mutated counterparts in ex-smokers. They suggest that the longer telomeres could mean that these cells have undergone fewer cell divisions and potentially represent descendants of dormant stem cells.

doi: 10.1038/s41586-020-1961-1

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