Once in a while, people are exposed to possibly detrimental substances in the environment or through their habits or diets. For instance, a compound discovered in cigarette and industrial smoke, benzo(a)pyrene (BaP), is responsible to damage DNA.
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Currently, scientists reporting in the journal ACS Central Science have mapped such effects—down to the single-nucleotide level—for the first time in human lung cells following BaP exposure. The researchers feel that this method could assist in predicting exposures that result in cancers.
When BaP enters a person’s body and is metabolized, it could get converted into a new compound or metabolite. This gets irreversibly attached to guanosine, which is one of the nucleic acids in DNA. But humans are also stocked with cellular repair kits that separate the undesirable metabolites.
Also, it is the balance present between damage and repair that tends to affect whether the mutations that could lead to disease carry forward when cells tend to replicate. Hence, Shana Sturla and collaborators wished to explore that balance in human lung cells that are exposed to BaP, identifying the distribution of DNA damage across the entire genomes of the cells.
Increasing amounts of the metabolized version of BaP were added by the scientists to the culture medium in which human lung cells were growing. Furthermore, the researchers identified where the metabolite was fixed to guanosines with the help of single-nucleotide-resolution DNA mapping.
Despite modifications in the BaP metabolite’s concentration, the pattern remained stable throughout the genome when there was a dose-dependent relationship between DNA damage and exposure.
Besides the outcomes implied that the distribution of DNA damage was quite identical to a mutation pattern discovered in smoking-related lung cancers. This denotes that this method could help predict genetic mutations concerned to human cancers.
Since the first single-nucleotide-resolution map of damage patterns particular to BaP in human cells, the scientists state their data offer good knowledge about the dynamic nature of DNA damage and also their repair processes.
Jiang, Y., et al. (2023) Quantification and Mapping of Alkylation in the Human Genome Reveal Single Nucleotide Resolution Precursors of Mutational Signatures. ACS Central Science. doi.org/10.1021/acscentsci.2c01100