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.