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Titolo:
A NIH 3T3 CELL-LINE STABLY EXPRESSING HUMAN CYTOCHROME P450-3A4 USED IN COMBINATION WITH A LACZ' SHUTTLE VECTOR TO STUDY MUTAGENICITY/
Autore:
DEGROENE EM; SEINEN W; HORBACH GJMJ;
Indirizzi:
UNIV UTRECHT,TOXICOL RES INST,YALELAAN 2,POB 80176 3508 TD UTRECHT NETHERLANDS
Titolo Testata:
European journal of pharmacology. Environmental toxicology and pharmacology section
fascicolo: 1, volume: 293, anno: 1995,
pagine: 47 - 53
SICI:
0926-6917(1995)293:1<47:AN3CSE>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
MAMMALIAN-CELLS; METABOLIC-ACTIVATION; HUMAN-LIVER; NIFEDIPINE OXIDASE; GENE MUTATION; CDNA; AFLATOXIN-B1; ENZYMES; DNA; COMPETENT;
Keywords:
CYTOCHROME P450-3A4, HUMAN; NIH/3T3 CELL; BIOTRANSFORMATION; LACZ' SHUTTLE VECTOR; MUTAGENICITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
E.M. Degroene et al., "A NIH 3T3 CELL-LINE STABLY EXPRESSING HUMAN CYTOCHROME P450-3A4 USED IN COMBINATION WITH A LACZ' SHUTTLE VECTOR TO STUDY MUTAGENICITY/", European journal of pharmacology. Environmental toxicology and pharmacology section, 293(1), 1995, pp. 47-53

Abstract

An NIH/3T3 cell line, stably expressing human cytochrome P450-3A4 (CYP3A4) cDNA has been developed. This cell line was used in combination with a shuttle vector, containing the bacterial lacZ' gene as reportergene, to study mutagenicity. Ethylmethanesulphonate and aflatoxin B-1were used as model agents to test this system. The mutation frequencyof ethylmethanesulphonate increased concentration dependently and wasthe same in CYP3A4-expressing cells as in parental NIH/3T3 cells, demonstrating that CYP3A4 activity has no influence on the mutagenicity of ethylmethanesulphonate. The mutation frequency of aflatoxin B-1 increased concentration dependently only in the CYP3A4-expressing cells and not in parental nor in vector-transfected cells. This increase in mutation frequency could be completely inhibited by ketoconazole, an inhibitor of cytochrome P450 activity, demonstrating the role of CYP3A4 in the activation of aflatoxin B-1. The system described in this paper opens the possibility to study the capacity of single human cytochromeP450s to activate xenobiotics into mutagenic metabolites. Since activation, phase II metabolism, DNA repair and an endpoint for mutations are all present in one cell, this system will be useful in screening aswell as in mechanistic studies.

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Documento generato il 27/01/20 alle ore 01:28:50