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

被引:14
作者
MaenhautMichel, G
JanelBintz, R
Samuel, N
Fuchs, RPP
机构
[1] POLE API ESBS,UPR 9003 CNRS,F-67400 ILLKIRCH GRAFFENS,FRANCE
[2] FREE UNIV BRUSSELS,DEPT BIOL MOL,LAB GENET PROCARYOTES,B-1640 RHODE ST GENESE,BELGIUM
来源
MOLECULAR & GENERAL GENETICS | 1997年 / 253卷 / 05期
关键词
food mutagens; Escherichia coli; SOS system; frameshift mutagenesis; slippage pathway;
D O I
10.1007/s004380050366
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:634 / 641
页数:8
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