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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
1989-6-8
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pubmed:abstractText |
We have isolated a human lymphoblastoid cell line with higher levels of native cytochrome P450IA1 activity and by DNA transfection introduced human cDNAs for a putative cytochrome P450IIA2 and epoxide hydrolase (E.C. 3.3.2.3). The resultant cell line, designated MCL-1, was substantially more sensitive to the mutagenicity of dimethylnitrosamine and benzo[a]pyrene than the AHH-1 cell line and was found to have increased metabolism of benzo[a]pyrene to dihydrodiols. The increase in native cytochrome P450IA1 activity was achieved by mutation and selection based on resistance to the phototoxicity of benzo[ghi]perylene. One resistant clone, designated L3, was used for subsequent studies. Two complete cDNAs, one encoding a putative cytochrome P450IIA2 and the other a microsomal epoxide hydrolase, were isolated from a human liver cDNA library. After introduction of the cDNAs into an expression vector and transfection into AHH-1 cells, gene expression was detected at the level of enzyme activity (epoxide hydrolase) or by increased sensitivity to dimethylnitrosamine cytotoxicity/mutagenicity (putative P450IIA2). A vector containing both cDNAs was then constructed and transfected into L3 cells to produce MCL-1 cells. The potential usefulness of drug-metabolizing gene transfection and of the MCL-1 cell line, in particular, for genetic toxicity testing is discussed.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Dimethylnitrosamine,
http://linkedlifedata.com/resource/pubmed/chemical/Epoxide Hydrolases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0143-3334
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
885-91
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:2706743-Benzo(a)pyrene,
pubmed-meshheading:2706743-Biotransformation,
pubmed-meshheading:2706743-Cell Line,
pubmed-meshheading:2706743-Cell Survival,
pubmed-meshheading:2706743-Cloning, Molecular,
pubmed-meshheading:2706743-Cytochrome P-450 Enzyme System,
pubmed-meshheading:2706743-DNA,
pubmed-meshheading:2706743-Dimethylnitrosamine,
pubmed-meshheading:2706743-Epoxide Hydrolases,
pubmed-meshheading:2706743-Humans,
pubmed-meshheading:2706743-Kinetics,
pubmed-meshheading:2706743-Restriction Mapping,
pubmed-meshheading:2706743-Transfection
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pubmed:year |
1989
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pubmed:articleTitle |
Development of a human cell line by selection and drug-metabolizing gene transfection with increased capacity to activate promutagens.
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pubmed:affiliation |
Gentest Corporation, Woburn, MA 01801.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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