ADDUCTS FORMED BY THE FOOD MUTAGEN 2-AMINO-3-METHYLIMIDAZO(4,5-F) QUINOLINE INDUCE FRAMESHIFT MUTATIONS AT HOT-SPOTS THROUGH AN SOS-INDEPENDENT PATHWAY

The potency of 2-amino-3-methylimidazo(4, 5-f)quinoline (IQ) adducts t o induce -2, -1 and +1 frameshift mutations has been determined on spe cific target DNA sequences, namely short runs of alternating GpC seque nces and short runs of guanines. The genetic control of the mutational processes has been analyzed using different Escherichia coli mutants, affected either in the control or in the mutagenesis pathway of the S OS system. We have shown that IQ adducts induce very efficiently both -1 and -2 frameshift mutations in E. coli. Both types of deletion muta tions are induced in bacteria without the need of SOS induction, indic ating that no LexA-controlled functions, in particular the UmuDC prote ins, are required for mutation fixation. We have also shown that the f requency of IQ-induced -2 frameshift mutations in alternating GC seque nces increases with the length of the repetition. The efficiency of IQ adducts to induce -1 and -2 frameshift mutations is similar to that o f N-2-acetylaminofluorene (AAF) adducts. Both chemicals are potent car cinogens which form covalent adducts at the C8 position of guanines. W e suggest that in both cases the adduct-induced DNA structure allows t he replication complex to perform a mutagenic bypass of the lesion by a slippage mechanism. However, in contrast to AAF-induced frameshift m utagenesis, IQ-induced frameshift mutagenesis is SOS-independent.