Idioma:

2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine-induced DNA adducts and genotoxicity in chinese hamster ovary (CHO) cells expressing human CYP1A2 and rapid or slow acetylator N-acetyltransferase 2

Metry, Kristin J. ; Zhao, Shuang ; Neale, Jason R. ; Doll, Mark A. ; States, J. Christopher ; McGregor, W. Glenn ; Pierce Jr, William M. ; Hein, David W.

Molecular carcinogenesis, 2007-07, Vol.46 (7), p.553-563 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Texto completo disponível

Citações Citado por

Enviar para

Título:
2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine-induced DNA adducts and genotoxicity in chinese hamster ovary (CHO) cells expressing human CYP1A2 and rapid or slow acetylator N-acetyltransferase 2
Autor: Metry, Kristin J. ; Zhao, Shuang ; Neale, Jason R. ; Doll, Mark A. ; States, J. Christopher ; McGregor, W. Glenn ; Pierce Jr, William M. ; Hein, David W.
Assuntos: 2-amino-1-methyl-6-phenylimidazo ; 2‐amino‐1‐methyl‐6‐phenylimidazo [4,5‐b] pyridine ; 5-b] pyridine ; Acetylation ; acetylator phenotype ; Animals ; Arylamine N-Acetyltransferase - genetics ; Arylamine N-Acetyltransferase - metabolism ; Carcinogens - toxicity ; CHO Cells - drug effects ; CHO Cells - metabolism ; Cricetinae ; Cricetulus ; Cytochrome P-450 CYP1A2 - genetics ; Cytochrome P-450 CYP1A2 - metabolism ; cytochrome P4501A2 ; DNA adducts ; DNA Adducts - metabolism ; DNA Damage ; Humans ; Imidazoles - metabolism ; Imidazoles - toxicity ; mutagenicity ; N-acetyltransferase 2 ; O-acetylation
É parte de: Molecular carcinogenesis, 2007-07, Vol.46 (7), p.553-563
Notas: ark:/67375/WNG-D9KJMLQQ-4
ArticleID:MC20302
istex:9CF15C4F5FB0D0C7AA89FF641B415823B9D4826C
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: Heterocyclic amine carcinogens such as 2‐amino‐1‐methyl‐6‐phenylimidazo [4,5‐b] pyridine (PhIP) are present in diet and cigarette smoke. Bioactivation in humans includes N‐hydroxylation catalyzed by cytochrome P4501A2 possibly followed by O‐acetylation catalyzed by N‐acetyltransferase 2 (NAT2). Nucleotide excision repair‐deficient Chinese hamster ovary (CHO) cells were stably transfected with human CYP1A2 and either NAT2*4 (rapid acetylator) or NAT2*5B (slow acetylator) alleles. CYP1A2 and NAT2 catalytic activities were undetectable in untransfected CHO cell lines. CYP1A2 catalytic activity levels did not differ significantly (P > 0.05) among the CYP1A2‐transfected cell lines. Cells transfected with NAT2*4 had significantly higher levels of N‐acetyltransferase (P = 0.0001) and N‐hydroxy‐PhIP O‐acetyltransferase (P = 0.0170) catalytic activity than cells transfected with NAT2*5B. PhIP caused dose‐dependent decreases in cell survival and significant (P < 0.001) increases in mutagenesis measured at the hypoxanthine phosphoribosyl transferase (hprt) locus in all the CYP1A2‐transfected cell lines. Transfection with NAT2*4 or NAT2*5B did not further increase hprt mutagenesis. PhIP‐induced hprt mutant cDNAs were sequenced, and 80% of the mutations were single base substitutions at G:C base pairs. dG‐C8‐PhIP DNA adduct levels were dose‐dependent in the order: untransfected < transfected with CYP1A2 < transfected with CYP1A2 and NAT2*5B < transfected with CYP1A2 and NAT2*4. Following incubation with 1.2 µM PhIP, DNA adduct levels were significantly (P < 0.05) higher in CHO cells transfected with CYP1A2/NAT2*4 versus CYP1A2/NAT2*5B. These results strongly support an activation role for CYP1A2 in PhIP‐induced mutagenesis and DNA damage and suggest a modest effect of human NAT2 and its genetic polymorphism on PhIP DNA adduct levels. © 2007 Wiley‐Liss, Inc.
Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Realização: Logos de Redes Sociais:

2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine-induced DNA adducts and genotoxicity in chinese hamster ovary (CHO) cells expressing human CYP1A2 and rapid or slow acetylator N-acetyltransferase 2

Metry, Kristin J. ; Zhao, Shuang ; Neale, Jason R. ; Doll, Mark A. ; States, J. Christopher ; McGregor, W. Glenn ; Pierce Jr, William M. ; Hein, David W.

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

Buscando em bases de dados remotas. Favor aguardar.