Persistent interferon signaling and clonal expansion mark early events in DNA methylation damage-induced liver cancer.

ABSTRACT: N-Nitrosodimethylamine (NDMA), a probable human carcinogen, induces toxic and mutagenic O ⁶-methylguanine lesions that are repaired by the O ⁶-methylguanine methyltransferase (MGMT). To elucidate mechanisms of NDMA-induced liver cancer progression, we performed longitudinal analyses of phenomic, transcriptomic, and phosphoproteomic changes in wild-type and MGMT-deficient mice, observing amplified responses in the deficient genotype. Early molecular rewiring indicative of a DNA damage response was detected by phosphoproteomic and transcriptomic profiling within days post-exposure. Transcriptomic analyses identified a persistent and robust interferon response as the dominant activated pathway. This chronic interferon signaling, which remained unresolved, c

SUBMITTER: Pribyl LJ 

PROVIDER: S-EPMC12621704 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature