Mapping of DNA damage from exposure to a compound in cigarettes, industrial smoke End-shutdown

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People are occasionally 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 reporting in ACS Central Sciences have mapped these effects, down to the single nucleotide level, for the first time in human lung cells after BaP exposure. They say this technique could help predict exposures that lead to cancer.

When BaP enters a person’s body and is metabolized, it can be turned into a new compound, or metabolite, that irreversibly binds to one of the nucleic acids in DNA, guanosine. However, humans also have cell repair kits that separate out unwanted metabolites. And it’s the balance between damage and repair that affects whether mutations that could cause disease continue when cells replicate. So Shana Sturla and her colleagues wanted to explore that balance in human lung cells exposed to BaP, determining the distribution of DNA damage across the cells’ entire genomes.

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

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

Quantification and mapping of alkylation in the human genome reveals single-nucleotide resolution precursors of mutational signatures, ACS Central Sciences (2023). DOI: 10.1021/accentsci.2c01100

Provided by the American Chemical Society

quotes: Mapping of DNA damage from exposure to a compound in cigarettes, industrial smoke (February 22, 2023) Retrieved February 22, 2023 from compound-cigarette-industrial.html

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