Document Detail


A metabolically competent human cell line expressing five cDNAs encoding procarcinogen-activating enzymes: application to mutagenicity testing.
MedLine Citation:
PMID:  1793807     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemical research in toxicology     Volume:  4     ISSN:  0893-228X     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:    1991 Sep-Oct
Date Detail:
Created Date:  1992-04-06     Completed Date:  1992-04-06     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  566-72     Citation Subset:  IM    
Affiliation:
Gentest Corporation, Woburn, Massachusetts 01801.
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MeSH Terms
Descriptor/Qualifier:
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:
N44-71001//PHS HHS
Chemical
Reg. No./Substance:
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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