Oxidative Stress Increases Frameshift Mutations in Human Colorectal Cancer Cells

摘要: Chronic inflammation in the gastrointestinal tract increases risk for development of cancer by an incompletely understood pathway, which may involve microsatellite instability (MSI). Low frequency MSI referred to as “MSI-L” occurs frequently chronically inflamed nonneoplastic tissue. In this work, we have tested hypothesis that oxidative stress induce accumulation frameshift mutations human DNA. Mismatch repair (MMR)-proficient HCT116+chr3 and MMR-deficient HCT116 cells were transfected with pCMV-(CA) 13 -EGFP, a plasmid contains (CA) dinucleotide repeat, disrupts reading frame downstream enhanced green fluorescent protein gene. A dose-dependent increase restoring was detected flow cytometry. At 1 mm H 2 O , mutant fraction 9-fold higher than mock-treated control cells. Although demonstrating stability at lower concentrations, MMR-proficient accumulated level (4.1-fold above control). No significant when pCMV-(N) 26 -EGFP construct nucleotides random sequence. These data indicate is potential mutagen leading contribute setting chronic inflammation.