Translesion Synthesis of N2 and C8-Deoxyguanosine Adducts of the Dietary Mutagen 2-Amino-3-methylimidazo-[4,5-f]-quinoline (IQ): Participation in Observed Mutagenic Spectra

Abstract

2-Amino-3-methylimidizo-[4,5-ʄ]-quinoline (IQ), a potent dietary mutagen, forms DNA adducts at the N² and C8-positions of 2ʹ-deoxyguanosine. IQ induces G to A transitions and G to T transversions in eukaryotic cells. The in vitro replication of the N²-dG-IQ and C8-dG-IQ adducts was examined by translesion DNA polymerases to determine their contributions to the observed mutagenic spectra. Our results implicate DNA polymerases kappa and eta in the error-free bypass of N2- and C8-dG-IQ adducts, respectively. In addition, DNA polymerase combinations eta/zeta and kappa/zeta are implicated in the mis-incorporation of A and T.