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Titolo:
GLUCURONIDATION OF CARCINOGENIC ARYLAMINES AND THEIR N-HYDROXY DERIVATIVES BY RAT AND HUMAN PHENOL UDP-GLUCURONOSYLTRANSFERASES OF THE UGT1GENE-COMPLEX
Autore:
ORZECHOWSKI A; SCHRENK D; BOCKHENNIG BS; BOCK KW;
Indirizzi:
UNIV TUBINGEN,INST TOXICOL,WILHELMSTR 56 D-72074 TUBINGEN GERMANY UNIV TUBINGEN,INST TOXICOL D-72074 TUBINGEN GERMANY
Titolo Testata:
Carcinogenesis
fascicolo: 8, volume: 15, anno: 1994,
pagine: 1549 - 1553
SICI:
0143-3334(1994)15:8<1549:GOCAAT>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
AROMATIC-AMINES; URINARY-BLADDER; HEMOGLOBIN ADDUCTS; LIVER; METABOLISM; 3-METHYLCHOLANTHRENE; 4-AMINOBIPHENYL; PARACETAMOL; MICROSOMES; SMOKING;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
A. Orzechowski et al., "GLUCURONIDATION OF CARCINOGENIC ARYLAMINES AND THEIR N-HYDROXY DERIVATIVES BY RAT AND HUMAN PHENOL UDP-GLUCURONOSYLTRANSFERASES OF THE UGT1GENE-COMPLEX", Carcinogenesis, 15(8), 1994, pp. 1549-1553

Abstract

Since carcinogenic arylamines are sequentially oxidized and conjugated with glucuronic acid, differences in glucuronidation may critically determine the toxic potential of these compounds. Therefore, N-glucuronidation of 1- and 2-naphthylamine (1-NA and 2-NA), 4-aminobiphenyl (4-ABP) and their N-hydroxy derivatives was investigated using rat and human liver microsomes and V79 cell-expressed phenol UDP-glucuronosyltransferases (UGT) of the UGT1 gene complex. Cell-expressed UGTs included rat and human UGT1.6, which are known to conjugate planar phenols, and human UGT1.7, conjugating both planar and bulky phenols. (i) N-Glucuronidation of 1- and 2-NA and of Nhydroxy-2-NA was inducible by 3-methylcholanthrene in rat liver microsomes whereas N-glucuronidation of the bulky arylamines CABP and N-hydroxy-4-ABP was not. In support of these findings mutagenicity of N-hydroxy-2-NA in the Ames test was markedly reduced upon addition of UDP-glucuronic acid using liver homogenates from 3-methylcholanthrene-treated rats. (ii) With cell-expressed rat UGT1.6, non-carcinogenic 1-NA was conjugated with the highest rate and with higher affinity than 2-NA. UGT1.6 showed poor activity towardsN-hydroxy-4-ABP and 4-ABP. (iii) Substrate specificity of human UGT1.6 also appeared to be limited to planar 1-NA, 2-NA and its N-hydroxy derivative, whereas UGT1.7 showed broader substrate specificity, including the bulky arylamine 4-ABP and its N-hydroxy derivative. The results suggest marked differences in substrate specificity of different UGTisozymes for arylamines and their N-hydroxy derivatives.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 09:36:56