Researchers have created the first single-nucleotide resolution map of damage patterns specific to benzo(a)pyrene (BaP) in human lung cells.
The study, reported in ACS Central Science, could help predict exposure to harmful substances that lead to cancers since BaP found in cigarette and industrial smoke is known to damage DNA.
A pedestrian smokes a cigarette while walking past buildings in the Euratlantique district of Bordeaux, southwestern France on October 19, 2022. - Bordeaux-Euratlantique is one of the sub-projects of the Bordeaux modernization program "Bordeaux 2030", an urban planning project started in 2009 part of the 738-hectare development centred on the Saint-Jean railway station, whose estimated end date is 2027.
BaP Exposure
When BaP enters a person's body, it has the ability to permanently connect to the guanosine, one of the nucleic acids in DNA. This may produce mutations that cause diseases, depending on how the body balances the processes of damage and repair, according to the research team's press release.
The team, under the direction of Shana Sturla, set out to look into the balance in human lung cells exposed to BaP. They exposed human lung cells to increasing concentrations of the metabolized form of BaP and used single-nucleotide-resolution DNA mapping to identify its damages.
The researchers found that the pattern of DNA damage remained stable across the genome, despite changes in the concentration of BaP metabolite. There was also a dose-dependent relationship between exposure and DNA damage.
The distribution of DNA damage was similar to a mutation pattern found in smoking-related lung cancers, suggesting that this technique could help predict genetic mutations related to human cancers.
The Swiss National Science Foundation and Philip Morris International have both provided funding to the authors.
Dynamic Nature of DNA Damage
The work emphasizes the dynamic nature of DNA damage and repair mechanisms and may aid in the early detection of cancer-causing exposures.
The study also shows the significance of maintaining a balance between damage and repair processes to prevent mutations that could result in diseases, even though humans have cellular repair kits that remove harmful metabolites.
The development of methods to lessen exposure to dangerous substances and the prevention of cancer-causing mutations could benefit from the findings of this study.
It illustrates how important it is to investigate how potentially dangerous compounds affect human cells in order to comprehend the molecular causes of disease.
The researchers claim that their findings offer insight into the dynamic nature of DNA damage and repair processes since they represent the first single-nucleotide-resolution map of damage patterns specific to BaP in human cells.
The study, titled "Quantification and Mapping of Alkylation in the Human Genome Reveal Single Nucleotide Resolution Precursors of Mutational Signatures", was published in ACS Central Science.
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