After sequencing individual lung cells in smokers, ex-smokers, and those who never smoked, the researchers compared the number of mutations in them. In the first group, this level was usually high, but ex-smokers showed many cells with a normal number of mutations - there were four times more of them than those who had not quit smoking yet. According to the authors of the article published in the journal Nature, these may be the descendants of cells that woke up after a person quit smoking.
By interacting with the cells of our lungs, carcinogens from tobacco smoke provoke a huge number of mutations, so that several thousand of them are found in the cancer cells of smokers. The share of mutations important for cancer is extremely small, but this is enough: around the world from this disease annually die about 1.8 million people, of which 80-90 percent are smokers. It is known that you can reduce your risk by quitting smoking, and this is especially effective in early or middle age. The benefits of quitting smoking appear almost immediately and gradually increase.
Kenichi Yoshida and his colleagues at the Cancer Genome Project found that this benefit was noticeable at the individual cell level: Quit smoking found a decent number of cells with a low mutational load. To find out, they sequenced the genomes of individual lung cells of 16 people, including smokers who quit and never smoked. They all had or suspected pulmonary carcinoma. This was the reason for the appointment of bronchoscopy, during which scientists were able to obtain cells for research. The sample of patients is small, but for each several dozen individual cells were sequenced, so that in total 632 samples were collected.
Mutational load - the number of accumulated mutations - varied greatly from cell to cell, both within groups and within individual patients. The number of substitutions depended on age - every year he threw in an average of 22 mutations - and smoking further increased this figure. The average number of substitutions among smokers was 5300 more than among healthy people, and among those who quit - by 2330 (p = 0, 0002). Despite such high average values, in the cell populations of former and current smokers, cells with a mutational load were found as in people who had never smoked, and the number of such cells was four times more in those who had tied up. In these patients, two groups of cells were clearly distinguished: with a high number of substitutions and with a normal one (and the latter were four times more likely to be found in those who quit smoking). In addition to the number of mutations, these two groups of cells differed in telomere length: they were longer in healthy cells.
Correlation of the number of substitutions and telomere length in patients' cells
How healthy cells survived after being bombarded with tobacco smoke and what allowed them to proliferate after a person quit smoking is not entirely clear. The long telomeres of these cells hint that these cells have gone through fewer cycles of division, and the authors speculate that they are descendants of recently awakened stem cells. The stage of the cell's life cycle determines its predisposition to the fixation of mutations. If a cell “slept” all the time while a person was smoking, and woke up to divide much later, then its mutational load will be less in comparison with the descendants of cells that were actively dividing during the smoking period.
Interestingly, the authors of the article did not find a relationship between the mutational load of lung cells and the intensity of smoking. The sample of patients is too small to investigate such an issue, but there are also larger studies on this topic in the literature. They argue that in terms of lung cancer and cardiovascular disease, smoking is very little different.