“Oxidative DNA Damage and Repair Disruption Under Pesticide–Metal Co‑Exposure”

Piperonyl butoxide (PBO) is an organic compound widely used as a pesticide synergist to enhance the efficacy of active ingredients like pyrethrins. While traditionally considered low-risk for mammals, recent evidence suggests its genotoxic potential may be underestimated, particularly in individuals with compromised DNA repair. This study investigated the DNA damage response triggered by PBO in a mammalian Chinese hamster ovary (CHO) cell model.

Immunofluorescent microscopy was used to track γH2AX foci, a sensitive marker for DNA double-strand breaks. To determine the mechanism of damage, EdU (5-ethynyl-2'-deoxyuridine) labeling was used to identify cells in the S-phase of the cell cycle. The study specifically compared standard CHO cells with PARP-deficient PADR9 cells to observe the effects of impaired repair mechanisms.

PBO treatment resulted in a significant, dose-dependent increase in γH2AX foci. These genotoxic effects were profoundly exacerbated in PARP-deficient PADR9 cells, which exhibited extensive pan-nuclear γH2AX signaling and widespread genomic instability. EdU incorporation confirmed that the observed DNA damage was predominantly S-phase dependent, identifying replication stress as the primary mechanism of PBO-induced toxicity.ConclusionsThese results reveal a previously underappreciated genotoxic pathway for PBO, demonstrating that substances labeled as low-risk can cause substantial genomic damage under compromised biological conditions. The specificity of this damage to DNA replication highlights a critical need to reassess the safety of PBO exposure, particularly for populations with genetic predispositions to impaired DNA repair.