Tobacco smoke carcinogens exacerbate APOBEC mutagenesis and carcinogenesis.

ABSTRACT: Mutations in somatic cells are inflicted by both extrinsic and intrinsic sources and contribute over time to cancer. Tobacco smoke contains chemical carcinogens that have been causatively implicated with cancers of the lung and head & neck^1,2. APOBEC family DNA cytosine deaminases have emerged as endogenous sources of mutation in cancer, with hallmark mutational signatures (SBS2/SBS13) that often co-occur in tumors of tobacco smokers with an equally diagnostic mutational signature (SBS4)^3,4. Here we challenge the dogma that mutational processes are thought to occur independently and with additive impact by showing that 4-nitroquinoline 1-oxide (NQO), a model carcinogen for tobacco exposure, sensitizes cells to APOBEC3B (A3B) mutagenesis and leads to synergistic increa

SUBMITTER: Durfee C 

PROVIDER: S-EPMC11785121 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature