3.4 Mutagenic potential of AFB1-FapyGua: COS7 cells versus E. coli
Investigations on mutagenic properties of AFB1-FapyGua in E. coli utilized the CXA sequence context (Smela et al. 2002). Comparison of these data with results of the present study demonstrated dramatically lower fidelity of replication bypass of AFB1-FapyGua in primate cells. While only three clones out of 30 analyzed had no mutations in this sequence context in our data set (Figure 2 ), sequences with the correct G at the target site were generated in E. coli at frequencies of ~90% under normal conditions or ~60% following induction of SOS response.
CONCLUSION
The mutagenic properties of the major AFB1-induced FapyGua adduct were assessed in primate cells using site-specifically modified vectors with the adduct being positioned in four different sequence contexts. Regardless of the context, AFB1-FapyGua was highly mutagenic, predominantly causing G > T transversions. These data provide further evidence for a primary role of this adduct in AFB1-induced mutagenesis. No correlation was apparent between the frequencies of AFB1-FapyGua-induced G > T transversions and the relative occurrences of these mutations in corresponding trinucleotide sequences following AFB1 exposure. Collectively, these data suggest a role of pre-replicative events in defining the mutational signature of AFB1.