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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
8
|
| pubmed:dateCreated |
1993-9-21
|
| pubmed:abstractText |
Transgenic Drosophila which carry a canine cytochrome P-450 were established and evaluated for its value on toxicology testing. Dah1, a cDNA clone for the canine hepatic P-4501A1, was ligated between the promoter of Drosophila heat-shock protein gene and the terminator of actin 5C gene, and then microinjected into Drosophila embryos with a transposon P element. The injected DNA was stably integrated into chromosomal DNA in germ line cells. After heat-shock treatments, transgenic larvae produced mRNA and a detectable amount of protein that cross-reacted with antibodies against rat P-4501A1. The ability of transgenic flies to activate procarcinogens was monitored in the DNA repair test with the endpoint being preadult mortality of repair-defective mei-9a mei-41D5/Y males. Heat-shock treatments of larvae showed that the repair-defective males carrying the P-4501A1 transgene were killed by lower concentrations of 7,12-dimethylbenz[a]anthracene than their non-transgenic or non heat-shocked counterparts. Coadministration of alpha-naphthoflavone, one of the inhibitors of P-4501A subfamily, cancelled the enhanced mortality of transgenic males, supporting that 7,12-dimethylbenz[a]anthracene was metabolized to its genotoxic form by the expressed P-4501A1 enzyme. This study indicates a potential utility of transgenic Drosophila for screening mammalian promutagens and procarcinogens.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0143-3334
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
14
|
| pubmed:geneSymbol |
P-450,
hsp70
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1683-8
|
| pubmed:dateRevised |
2008-11-21
|
| pubmed:meshHeading |
pubmed-meshheading:8353852-9,10-Dimethyl-1,2-benzanthracene,
pubmed-meshheading:8353852-Animals,
pubmed-meshheading:8353852-Animals, Genetically Modified,
pubmed-meshheading:8353852-Biotransformation,
pubmed-meshheading:8353852-Cytochrome P-450 Enzyme System,
pubmed-meshheading:8353852-DNA,
pubmed-meshheading:8353852-DNA Damage,
pubmed-meshheading:8353852-DNA Repair,
pubmed-meshheading:8353852-Dogs,
pubmed-meshheading:8353852-Drosophila,
pubmed-meshheading:8353852-Drug Evaluation, Preclinical,
pubmed-meshheading:8353852-Female,
pubmed-meshheading:8353852-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:8353852-Hot Temperature,
pubmed-meshheading:8353852-Isoenzymes,
pubmed-meshheading:8353852-Male,
pubmed-meshheading:8353852-Pedigree,
pubmed-meshheading:8353852-Toxicology
|
| pubmed:year |
1993
|
| pubmed:articleTitle |
Transgenic Drosophila carrying mammalian cytochrome P-4501A1: an application to toxicology testing.
|
| pubmed:affiliation |
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|