The role of DNA repair in benzene-induced carcinogenesis

Benzene is a well-known human carcinogen, but the ultimate mode of action is still not known. Several reactive metabolites have been identified, including benzene oxide, phenol, hydrochinone, catechol and benzoquinones, generating different types of DNA lesions. Furthermore, the latter three metabolites may lead to the formation of reactive oxygen species (ROS) due to redox cycling, which give rise to oxidative DNA lesions and altered signaling pathways. Also, the inhibition of DNA topoisomerase II may result in DNA double strand breaks. Even though the exact contribution of the respective metabolites to benzene-induced carcinogenicity is not yet resolved, the major DNA repair pathways such as base excision repair (BER), nucleotide excision repair (NER) and double strand break (DSB) repair are involved in the removal of benzene-induced DNA lesions. The observed target organ specificity may result from increased adduct formation, but also from poor repair in bone marrow progenitor cells. While especially excision repair pathways are predominantly error-free and thus protective, DSB repair is largely error prone and may contribute to benzene-induced genomic instability.