| A metabolically competent human cell line expressing five cDNAs encoding procarcinogen-activating enzymes: application to mutagenicity testing. | |
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MedLine Citation:
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PMID: 1793807 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A human B-lymphoblastoid cell line, designated MCL-5, constitutively expressing human cytochrome P-450 CYP1A1 and also expressing five transfected human cDNAs encoding drug-metabolizing enzymes, has been developed. cDNAs encoding CYP1A2, CYP2A6, and microsomal epoxide hydrolase (mEH) were introduced by using a vector conferring hygromycin B resistance, and cDNAs encoding CYP2E1 and CYP3A4 were introduced by using a vector conferring resistance to 1-histidinol. MCL-5 cells stably expressed all five cDNAs and the native CYP1A1 as determined by measurement of form-specific enzyme activity levels. The mutagenicity of seven model procarcinogens to MCL-5 cells was examined at the hypoxanthine guanine phosphoribosyltransferase (hprt) and thymidine kinase (tk) loci. Exposure to benzo[a]pyrene (BP), 3-methylcholanthrene (3MC), N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), aflatoxin B1, (AFB1), 2-(acetylamino)fluorene (AAF), or benzidine (BZD) induced a statistically significant increase in mutant frequency. Linear interpolation of the concentration of procarcinogen necessary to produce a doubling of the mutant fraction at the hprt locus in MCL-5 cells and the parent AHH-1 cell line revealed that, for each of the chemicals examined, except BZD, MCL-5 cells were significantly more sensitive than the parent AHH-1 cells. The increase in sensitivity to mutagenicity ranged from 3-fold for AAF to greater than 40,000-fold for NDMA. MCL-5 cells have great potential as a screening system for the analysis of human procarcinogen/promutagen activation. |
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Authors:
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C L Crespi; F J Gonzalez; D T Steimel; T R Turner; H V Gelboin; B W Penman; R Langenbach |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Chemical research in toxicology Volume: 4 ISSN: 0893-228X ISO Abbreviation: Chem. Res. Toxicol. Publication Date: 1991 Sep-Oct |
Date Detail:
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Created Date: 1992-04-06 Completed Date: 1992-04-06 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8807448 Medline TA: Chem Res Toxicol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 566-72 Citation Subset: IM |
Affiliation:
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Gentest Corporation, Woburn, Massachusetts 01801. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Carcinogenicity Tests Carcinogens / metabolism* Cell Line Cytochrome P-450 Enzyme System / biosynthesis*, genetics DNA / biosynthesis* Enzyme Activation Humans Immunoblotting Microsomes / enzymology Mutagenicity Tests / methods* Transfection Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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N44-71001//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Carcinogens; 9007-49-2/DNA; 9035-51-2/Cytochrome P-450 Enzyme System |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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