Mechanism of biochanin A alleviating PM2.5-induced oxidative damage based on an XRCC1 knockout BEAS-2B cell model

PM2.5 induces oxidative/antioxidant system imbalance and excessive release of reactive oxygen species (ROS) and produces toxic effects and irreversible damage to the genetic material including chromosomes and DNA. Biochanin A (BCA), an isoflavone with strong antioxidant activity, effectively intervenes against PM2.5-induced oxidative damage. The X-ray repair cross-complementary protein 1 (XRCC1)/BER pathway involves DNA damage repair caused by oxidative stress. This paper aims to explore the mechanism of BCA alleviating oxidative DNA damage caused by PM2.5 by establishing the in vitro cell model based on CRISPR/Cas9 technology and combining it with mechanism pathway research. The results showed that PM2.5 exposure inhibited the expression of BER and NER pathway proteins and induced the overexpression of ERCC1. BCA showed an effective intervention in the toxicity of PM2.5 in normal cells, rather than XRCC1 knock-out cells. This laid a foundation for further exploring the key role of XRCC1 in PM2.5-caused oxidative damage and the BER/DNA damage repair pathway.