Mapping DNA damage from exposure to a compound in cigarettes, industrial smoke

Sometimes people are exposed to potentially harmful substances in the environment or through their diets or habits. For example, a compound found in cigarettes and industrial smoke, benzo(a)pyrene (BaP), is known to damage DNA. Now, researchers are reporting i ACS Central Science They have mapped these effects — down to the single-nucleotide level — for the first time in human lung cells after BP exposure. They say this technique could help predict exposures that lead to cancers.

When BaP enters a person’s body and is metabolized, it can turn into a new compound, or metabolite, that binds irreversibly to one of the nucleic acids in DNA, guanosine. However, humans also have cellular repair equipment that breaks down the unwanted metabolites. And the balance between damage and repair affects whether replicating cells carry the mutations that can cause disease. So, Shana Sturla and colleagues wanted to explore that balance in human lung cells exposed to BaP, determining the distribution of DNA damage throughout the cells’ entire genomes.

The researchers added increasing amounts of the metabolized version of BaP to the culture medium in which human lung cells were growing. They then determined where the metabolite was attached to guanosines using single-nucleotide-resolution DNA mapping. Although there was a dose-dependent relationship between exposure and DNA damage, the pattern remained stable throughout the genome, despite changes in the concentration of the BaP metabolite.

In addition, the results showed that the distribution of DNA damage was similar to the pattern of mutations found in smoking-related lung cancers, suggesting that this technique could help predict genetic mutations associated with human cancer. As the first single-nucleotide resolution map of BaP-specific damage patterns in human cells, the researchers say their data provide insight into the dynamic nature of DNA damage and repair processes.