The Human Carcinogen Aristolochic Acid I Is Activated to Form DNA Adducts by Human NAD(P)H:quinone Oxidoreductase Without the Contribution of Acetyltransferases or Sulfotransferases

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F11%3A10100373" target="_blank" >RIV/00216208:11310/11:10100373 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11130/11:7041

Výsledek na webu

<a href="http://dx.doi.org/10.1002/em.20642" target="_blank" >http://dx.doi.org/10.1002/em.20642</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/em.20642" target="_blank" >10.1002/em.20642</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The Human Carcinogen Aristolochic Acid I Is Activated to Form DNA Adducts by Human NAD(P)H:quinone Oxidoreductase Without the Contribution of Acetyltransferases or Sulfotransferases

Popis výsledku v původním jazyce

Ingestion of aristolochic acid (AA) is associated with development of urothelial tumors linked with AA nephropathy and is implicated in the development of Balkan endemic nephropathy-associated urothelial tumors. We investigated the efficiency of human NAD(P)H:quinone oxidoreductase (NQO1) to activate aristolochic acid I (AAI) and used in silico docking, using soft-soft (flexible) docking procedure, to study the interactions of AAI with the active site of human NQO1. AAI binds to the active site of NQO1indicating that the binding orientation allows for direct hydride transfer (i.e., two electron reductions) to the nitro group of AAI. NQO1 activated AAI, generating DNA adduct patterns reproducing those found in urothelial tissues from humans exposed toAA. Because reduced aromatic nitro-compounds are often further activated by sulfotransferases (SULTs) or N,O-acetlytransferases (NATs), their roles in AAI activation were investigated. Our results indicate that phase II reactions do not p

Název v anglickém jazyce

The Human Carcinogen Aristolochic Acid I Is Activated to Form DNA Adducts by Human NAD(P)H:quinone Oxidoreductase Without the Contribution of Acetyltransferases or Sulfotransferases

Popis výsledku anglicky

Ingestion of aristolochic acid (AA) is associated with development of urothelial tumors linked with AA nephropathy and is implicated in the development of Balkan endemic nephropathy-associated urothelial tumors. We investigated the efficiency of human NAD(P)H:quinone oxidoreductase (NQO1) to activate aristolochic acid I (AAI) and used in silico docking, using soft-soft (flexible) docking procedure, to study the interactions of AAI with the active site of human NQO1. AAI binds to the active site of NQO1indicating that the binding orientation allows for direct hydride transfer (i.e., two electron reductions) to the nitro group of AAI. NQO1 activated AAI, generating DNA adduct patterns reproducing those found in urothelial tissues from humans exposed toAA. Because reduced aromatic nitro-compounds are often further activated by sulfotransferases (SULTs) or N,O-acetlytransferases (NATs), their roles in AAI activation were investigated. Our results indicate that phase II reactions do not p

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)

Rok uplatnění

2011

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Environmental and Molecular Mutagenesis

ISSN

0893-6692

e-ISSN

—

Svazek periodika

52

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

448-459

Kód UT WoS článku

000293250700003

EID výsledku v databázi Scopus

—