In a first, scientists map cigarette and industrial smoke effects on DNA
It is common knowledge that people are exposed to harmful substances in the environment or through their diets. For instance, benzo(a)pyrene (BaP), a compound found in cigarette and industrial smoke, is known to damage DNA.
BaP is part of the group of compounds known as polycyclic aromatic hydrocarbons (PAHs). Now, PAHs are produced when organic material is burned incompletely or heated. For example, exhaust fumes from diesel vehicles and smoke from wood stoves contain PAHs. One of the most important causes of cancer can be attributed to exposure to PAHs, due to high exposure.
In our body, enzymes help break down PAHs, which in turn damages DNA. And if the damage cannot be repaired, it develops into cancer.
Now, for the first time, researchers reporting in ACS Central Science have mapped these effects down to the single-nucleotide level in human lung cells after BaP exposure, as per a press release. According to them, this technique could help predict exposures that lead to cancers.
The first single-nucleotide-resolution map of damage patterns specific to BaP
When BaP gets into a human body, it is metabolized and turns into a new compound that attaches itself to one of the nucleic acids in DNA called guanosine. Though irreversible, humans also contain cellular repair kits that could detach unwanted metabolites.
But, it is the balance between damage and repair that largely impacts the mutations that could cause disease to carry forward when cells are replicated.
Professor Shana Sturla and colleagues wanted to investigate the balance in human cells exposed to BaP and determine the distribution of DNA damage throughout the cells' entire genomes.
They created a culture medium in which human lung cells were being grown. To this, the researchers added increasing amounts of the metabolized version of BaP. After which, they could determine where the metabolite is attached to guanosines using single-nucleotide-resolution DNA mapping.
The data could provide insight into the dynamic nature of DNA damage
Though there was a "dose-dependent" relationship between exposure and DNA damage, "the pattern remained stable across the genome, despite changes in the BaP metabolite’s concentration".
The team noticed that the distribution of DNA damage was similar to a mutation pattern found in smoking-related lung cancers - this suggested that this very technique could help forecast genetic mutations related to human cancers.
Considering that this is the first single-nucleotide-resolution map of damage patterns specific to BaP in human cells, the researchers said their "data could provide insight into the dynamic nature of DNA damage and repair processes".