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Statements

Subject Item
n2:RIV%2F00216208%3A11310%2F14%3A10282815%21RIV15-MSM-11310___
rdf:type
n5:Vysledek skos:Concept
rdfs:seeAlso
http://dx.doi.org/10.3390/ijms150610271
dcterms:description
This review summarizes the results found in studies investigating the enzymatic activation of two genotoxic nitro-aromatics, an environmental pollutant and carcinogen 3-nitrobenzanthrone (3-NBA) and a natural plant nephrotoxin and carcinogen aristolochic acid I (AAI), to reactive species forming covalent DNA adducts. Experimental and theoretical approaches determined the reasons why human NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P450 (CYP) 1A1 and 1A2 have the potential to reductively activate both nitro-aromatics. The results also contributed to the elucidation of the molecular mechanisms of these reactions. The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs) and sulfotransferases (SULTs) to the activation of 3-NBA and AAI was also examined. The results indicated differences in the abilities of 3-NBA and AAI metabolites to be further activated by these conjugation enzymes. The formation of DNA adducts generated by both carcinogens during their reductive activation by the NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in subcellular cytosolic and microsomal fractions, selective inhibitors, and animal models (including knock-out and humanized animals). For the theoretical approaches, flexible in silico docking methods as well as ab initio calculations were employed. The results summarized in this review demonstrate that a combination of experimental and theoretical approaches is a useful tool to study the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction. This review summarizes the results found in studies investigating the enzymatic activation of two genotoxic nitro-aromatics, an environmental pollutant and carcinogen 3-nitrobenzanthrone (3-NBA) and a natural plant nephrotoxin and carcinogen aristolochic acid I (AAI), to reactive species forming covalent DNA adducts. Experimental and theoretical approaches determined the reasons why human NAD(P)H:quinone oxidoreductase (NQO1) and cytochromes P450 (CYP) 1A1 and 1A2 have the potential to reductively activate both nitro-aromatics. The results also contributed to the elucidation of the molecular mechanisms of these reactions. The contribution of conjugation enzymes such as N,O-acetyltransferases (NATs) and sulfotransferases (SULTs) to the activation of 3-NBA and AAI was also examined. The results indicated differences in the abilities of 3-NBA and AAI metabolites to be further activated by these conjugation enzymes. The formation of DNA adducts generated by both carcinogens during their reductive activation by the NOQ1 and CYP1A1/2 enzymes was investigated with pure enzymes, enzymes present in subcellular cytosolic and microsomal fractions, selective inhibitors, and animal models (including knock-out and humanized animals). For the theoretical approaches, flexible in silico docking methods as well as ab initio calculations were employed. The results summarized in this review demonstrate that a combination of experimental and theoretical approaches is a useful tool to study the enzyme-mediated reaction mechanisms of 3-NBA and AAI reduction.
dcterms:title
Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches
skos:prefLabel
Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches Mechanisms of Enzyme-Catalyzed Reduction of Two Carcinogenic Nitro-Aromatics, 3-Nitrobenzanthrone and Aristolochic Acid I: Experimental and Theoretical Approaches
skos:notation
RIV/00216208:11310/14:10282815!RIV15-MSM-11310___
n3:aktivita
n4:P n4:I
n3:aktivity
I, P(GA14-18344S)
n3:cisloPeriodika
6
n3:dodaniDat
n13:2015
n3:domaciTvurceVysledku
n6:8486573 n6:3062465
n3:druhVysledku
n18:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n20:predkladatel
n3:idSjednocenehoVysledku
28138
n3:idVysledku
RIV/00216208:11310/14:10282815
n3:jazykVysledku
n10:eng
n3:klicovaSlova
cytochrome; NAD(P)H:quinone oxidoreductase; molecular modeling; DNA adducts; aristolochic acid I; 3-nitrobenzanthrone; nitro-aromatics
n3:klicoveSlovo
n9:cytochrome n9:DNA%20adducts n9:molecular%20modeling n9:aristolochic%20acid%20I n9:NAD%28P%29H%3Aquinone%20oxidoreductase n9:3-nitrobenzanthrone n9:nitro-aromatics
n3:kodStatuVydavatele
CH - Švýcarská konfederace
n3:kontrolniKodProRIV
[55945C015B54]
n3:nazevZdroje
International Journal of Molecular Sciences
n3:obor
n19:CE
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
5
n3:projekt
n15:GA14-18344S
n3:rokUplatneniVysledku
n13:2014
n3:svazekPeriodika
15
n3:tvurceVysledku
Frei, Eva Stiborová, Marie Schmeiser, Heinz H. Arlt, Volker M. Martínek, Václav
n3:wos
000338639000065
s:issn
1422-0067
s:numberOfPages
25
n8:doi
10.3390/ijms150610271
n17:organizacniJednotka
11310