POLE Deficiency Exacerbates Diesel Engine Exhaust-Induced Genomic Instability and Malignant Transformation of Bronchial Epithelial Cells.

ABSTRACT: Diesel engine exhaust (DEE) is classified as a Group I carcinogen, yet direct experimental evidence that DEE induce carcinogenesis is lacking. Here, it is innovatively discovered that 120 µg mL^-1 DEE exposure for 20 weeks, original bronchial epithelial cells exhibit abnormal morphology, form colonies in soft agar, and readily develop the lumps under the subcutaneous tissue of immunodeficient mice, which are pathologically confirmed as lung squamous cell carcinoma. Whole genome sequencing and RNA sequencing identify DEE-induced mutational signatures (DBS3, ID1/ID2), associated with polymerase epsilon (POLE) exonuclease domain mutations and mismatch repair (MMR) deficiency. Besides, 52 exonic mutations, 734 copy number variations (CNVs), and 2519 differentially expressed genes (DE

SUBMITTER: Zhang P 

PROVIDER: S-EPMC12463065 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature