Benzo[a]pyrene increases DNA double strand break repair in vitro and in vivo: A possible mechanism for benzo[a]pyrene-induced toxicity

•Examination of BaP-induced DNA double strand breaks and repair activation was investigated.•BaP-induced increased homologous recombinational DNA repair in CHO 3–6 cells.•BaP-induced increased positive staining for recombination events in the lung and thymus of exposed pKZ1 animals.•BaP decreased gene expression of ATM and Xrcc6 in liver and lung from treated mice.•BaP reduced expression of Xrcc5, p53, and DNA-PKcs in lung from treated mice.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon and carcinogen that is released into the environment through natural and anthropogenic sources. BaP toxicity is dependent on its metabolism by cytochrome P450s to the reactive metabolite benzo[a]pyrene diol epoxide (BPDE), which is strongly associated with increased mutation frequency. BaP can also be metabolized to benzo[a]pyrene quinones that can undergo redox cycling and induce oxidative stress. The purpose of this study was to examine if BaP exposure induces DNA double strand breaks (DSBs) and subsequently activate DNA DSB repair pathways in the CHO 3–6 cell line and pKZ1 mouse model. In vitro assessment of homologous recombination (HR) showed significantly increased HR frequency following exposure to 10 μM of BaP. In vivo evaluations of BaP-induced DNA DSB repair demonstrated positive staining for intrachromosomal recombination events, which