Cell-free chromatin particle (cfChP)

Cell-free chromatin particles (cfChPs) are fragments of DNA and histones released into the circulation and extracellular space during cell death via apoptosis or necrosis (Mittra et al., 2012, J. Biosci.). These particles act as damage-associated molecular patterns (DAMPs), capable of entering healthy cells to induce double-strand DNA breaks, genomic instability, and inflammatory cytokine production (Mittra et al., 2015, Ann. Oncol.). In oncology, cfChPs are implicated in the progression of metastasis and the development of therapy-related toxicities by damaging healthy tissue (Inderjit et al., 2021, Front. Genet.). In acute inflammatory states like sepsis and COVID-19, elevated levels of cfChPs contribute to the cytokine storm and multi-organ dysfunction (Raghuram et al., 2021, PLoS One). Therapeutic interventions aim to degrade these particles using DNase I or a combination of Resveratrol and Copper (R-Cu), which generates oxygen radicals to destroy the chromatin structure (Mittra et al., 2017, Free Radic. Biol. Med.). Such treatments have shown promise in reducing systemic inflammation and preventing cancer recurrence in preclinical models. Beyond cancer and sepsis, cfChPs are being investigated for their role in autoimmune diseases and diabetes-related complications (Pal et al., 2021, Sci. Rep.).

Other names

Extracellular DNACell-free DNAcfDNACirculating nucleosomeExtracellular fragmented DNAecDNACirculating chromatin

Enzymatic or oxidative degradation of extracellular DNA and histone components to neutralize their activity as damage-associated molecular patterns (DAMPs) and prevent their uptake by healthy cells.