Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

被引:33
作者
Abril, N
LuqueRomero, FL
PrietoAlamo, MJ
Rafferty, JA
Margison, GP
Pueyo, C
机构
[1] UNIV CORDOBA,DEPT BIOQUIM & BIOL MOL,E-14071 CORDOBA,SPAIN
[2] CHRISTIE HOSP NHS TRUST,PATERSON INST CANC RES,CRC,DEPT CARCINOGENESIS,MANCHESTER M20 9BX,LANCS,ENGLAND
关键词
D O I
10.1093/carcin/18.10.1883
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O-6-alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene, We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity, We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt(-) ada(-) E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid, Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector-transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat, Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O-6-methylguanine binding domain of the protein, The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM, The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound, T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase, The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt(-) ada(-) cells showed no effect, in spite of the reported potential of bioactive dihaloethane-derived species to alkylate Trx.
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页码:1883 / 1888
页数:6
相关论文
共 51 条
[11]   Novel human DNA alkyltransferases obtained by random substitution and genetic selection in bacteria [J].
Christians, FC ;
Loeb, LA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (12) :6124-6128
[12]  
CMARIK JL, 1992, J BIOL CHEM, V267, P6672
[13]  
DAVIS RW, 1980, ADV BACTERIAL GENET, P201
[14]  
FISHBEIN L, 1985, IARC SCI PUBLICATION, V68
[15]   AN ANALYSIS OF THE MUTAGENICITY OF 1,2-DIBROMOETHANE TO ESCHERICHIA-COLI - INFLUENCE OF DNA-REPAIR ACTIVITIES AND METABOLIC PATHWAYS [J].
FOSTER, PL ;
WILKINSON, WG ;
MILLER, JK ;
SULLIVAN, AD ;
BARNES, WM .
MUTATION RESEARCH, 1988, 194 (03) :171-181
[16]  
Friedberg E.C., 1995, DNA REPAIR
[17]   CONSTRUCTION OF A FAMILY OF UNIVERSAL EXPRESSION PLASMID VECTORS [J].
HANNA, Z ;
FREGEAU, C ;
PREFONTAINE, G ;
BROUSSEAU, R .
GENE, 1984, 30 (1-3) :247-250
[18]  
HOLMGREN A, 1989, J BIOL CHEM, V264, P13963
[19]   CLONING AND EXPRESSION OF THE GLUTAREDOXIN (GRX) GENE OF ESCHERICHIA-COLI [J].
HOOG, JO ;
VONBAHRLINDSTROM, H ;
JORNVALL, H ;
HOLMGREN, A .
GENE, 1986, 43 (1-2) :13-21
[20]   MUTATIONAL SPECIFICITY OF ALKYLATING-AGENTS AND THE INFLUENCE OF DNA-REPAIR [J].
HORSFALL, MJ ;
GORDON, AJE ;
BURNS, PA ;
ZIELENSKA, M ;
VANDERVLIET, GME ;
GLICKMAN, BW .
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, 1990, 15 (02) :107-122