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 to induce -2, -1 and +1 frameshift mutations has been determined on specific target DNA sequences, namely short runs of alternating GpC sequences 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 SOS system. We have shown that IQ adducts induce very efficiently both -1 and -2 frameshift mutations in E. coli. Both types of deletion mutations are induced in bacteria without the need of SOS induction, indicating that no LexA-controlled functions, in particular the UmuDC proteins, are required for mutation fixation. We have also shown that the frequency of IQ-induced -2 frameshift mutations in alternating GC sequences increases with the length of the repetition. The efficiency of IQ adducts to induce -1 and -2 frameshift mutations is similar to that of N-2-acetylaminofluorene (AAF) adducts. Both chemicals are potent carcinogens which form covalent adducts at the C8 position of guanines. We suggest that in both cases the adduct-induced DNA structure allows the replication complex to perform a mutagenic bypass of the lesion by a slippage mechanism. However, in contrast to AAF-induced frameshift mutagenesis, IQ-induced frameshift mutagenesis is SOS-independent.
Maenhaut-Michel
G
G
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
Janel-Bintz
R
R
Samuel
N
N
Fuchs
R P
RP
D018736:DNA Adducts; D018900:Dinucleotide Repeats; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D016368:Frameshift Mutation; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D013014:SOS Response, Genetics
D018736:DNA Adducts; C096278:DNA-(2-amino-3-methylimidazo(4,5-f)quinoline) adduct; D009153:Mutagens; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline