Formation and Repair of Tobacco Carcinogen-Derived Bulky DNA Adducts

Figure 4

Multiple benzene metabolites, different types of DNA lesions, and proposed biological effects. Benzene has a complex metabolism and the listed metabolites are not a complete list. The adducts formed include those identified in vitro and in vivo, stable and unstable, bulky and oxidized adducts. DSBs are one of the most severe DNA lesions caused directly and indirectly by benzene metabolites. Repair of benzene-DNA adducts may include multiple mechanisms such as BER, NER, and NIR. Only those adducts that finally escape all the defense mechanisms such as repair, or are misrepaired, may lead to mutations. Persistence or coexistence of different types of lesions could form a broad-based attack on the genomic stability. It is also known that a number of benzene metabolites can inhibit topoisomerase II (topo II) activity, which may represent a potential mechanism for benzene’s clastogenic effects [326].