DNA Damage Map Reveals Mutational Signature Stemming From Carcinogenic Compound

Swiss researchers reporting in the journal ACS Central Science describe DNA damage patterns associated with a carcinogenic compound called benzo(a)pyrene (BaP), which has been found in everything from foods or cigarettes to coal tar or industrial smoke. Using a sequencing strategy developed to find DNA damage with single-nucleotide resolution — coupled with quantitative mass spectrometry profiling — the team did dose-response mapping of BaP-related, alkylation-derived DNA adducts that formed in a human lung cancer line when BaP metabolites interact with guanosine, identifying a BaP damage signature that resembled smoking-related signatures found in lung cancer in the past. When the authors analyzed BaP-related DNA damage in relation to predicted transcription and chromatin accessibility patterns, meanwhile, they found that BaP exposure levels, chromatin state, and transcriptional features all appeared to contribute to DNA adduct levels. "Genome-wide distribution of profiles of DNA alkylation adducts as potentially predictive markers of carcinogenic hazards have not been widely investigated," they write, noting that the study "provides the first single-nucleotide resolution map of damage patterns specific to the human carcinogen BaP in human cells."