Mutagenic action of 5-nitroimidazoles:: in vivo induction of GC→CG transversion in two Bacteroides fragilis reporter genes

被引:24
作者
Trinh, S [1 ]
Reysset, G [1 ]
机构
[1] Inst Pasteur, Unite Anaerobies, F-75724 Paris 15, France
关键词
Bacteroides fragilis; 5-nitroimidazole; metronidazole; dimetridazole; tetQ gene; nimA gene; mutation; transversion;
D O I
10.1016/S0027-5107(97)00240-6
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The in vivo mutagenic potential of two 5-nitroimidazoles, metronidazole and dimetridazole, was evaluated in Bacteroides fragilis, a strictly anaerobic bacterium. Two antibiotic resistance genes, tetA(Q)3 and nimA, were used as DNA targets. The forward and back mutations were identified by nucleotide sequence analysis. Both drugs induced GC --> CG transversion exclusively. The results suggest that the reactive molecules generated during the intracellular reduction of the 5-nitroimidazoles are responsible for both base pair substitutions and DNA strand breaks, although the mechanisms and targets may be different. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:55 / 65
页数:11
相关论文
共 29 条
[1]  
BIRNBOIM HC, 1979, NUCLEIC ACIDS RES, V7, P1513
[2]  
CANTELLIFORTI G, 1983, TERATOGEN CARCIN MUT, V3, P51, DOI 10.1002/1520-6866(1990)3:1<51::AID-TCM1770030107>3.0.CO
[3]  
2-L
[4]   SCREENING FOR MUTAGENICITY OF NITRO-GROUP CONTAINING HYPOXIC CELL RADIOSENSITIZERS USING SALMONELLA-TYPHIMURIUM STRAINS-TA100 AND STRAINS-TA98 [J].
CHIN, JB ;
SHEININ, DMK ;
RAUTH, AM .
MUTATION RESEARCH, 1978, 58 (01) :1-10
[5]   PHYSIOLOGICAL-EFFECTS OF METRONIDAZOLE ON CLOSTRIDIUM-PASTEURIANUM [J].
CHURCH, DL ;
BRYANT, RD ;
RABIN, HR ;
LAISHLEY, EJ .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1991, 28 (02) :221-228
[6]  
DECLERCK PJ, 1986, BIOCHEM PHARMACOL, V35, P59, DOI 10.1016/0006-2952(86)90555-1
[7]   BASE SPECIFIC INTERACTION OF REDUCTIVELY ACTIVATED NITROIMIDAZOLES WITH DNA [J].
DECLERCK, PJ ;
DERANTER, CJ ;
VOLCKAERT, G .
FEBS LETTERS, 1983, 164 (01) :145-148
[8]   GENOTOXICITY AND CARCINOGENICITY OF METRONIDAZOLE [J].
DOBIAS, L ;
CERNA, M ;
ROSSNER, P ;
SRAM, R .
MUTATION RESEARCH, 1994, 317 (03) :177-194
[9]  
Edwards D. I., 1980, The host-invader interplay. (Proc. 3rd Internat. Symp. on the biochemistry of parasites and host-parasite relationships, Beerse, Belgium, 30 June to 3 July 1980.), P673
[10]   NITROIMIDAZOLE DRUGS - ACTION AND RESISTANCE MECHANISMS .1. MECHANISMS OF ACTION [J].
EDWARDS, DI .
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 1993, 31 (01) :9-20