Source:http://linkedlifedata.com/resource/pubmed/id/10067811
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
1999-4-28
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pubmed:abstractText |
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) results in a broad spectrum of biological responses, including altered metabolism, disruption of normal hormone signaling pathways, reproductive and developmental effects, and cancer. Cytochrome P450 1B1 (CYP1B1) is a dioxin-inducible gene that is active in the formation of 4-hydroxyestradiol, a potentially genotoxic catechol estrogen. Therefore, the analysis of CYP1B1 in humans may be useful in establishing relationships between dioxin exposure and adverse health effects. In this study, we examined the expression of CYP1B1 in human peripheral blood lymphocytes of unexposed individuals using a quantitative reverse transcription-PCR method. Absolute CYP1B1 RNA levels varied more than 30-fold in uncultured mononuclear cells obtained from 10 individuals. In vitro treatment of mitogen-stimulated lymphocytes with TCDD for 1-5 days of culture resulted in a peak induction of CYP1B1 after 3 days. The induction of CYP1B1 RNA levels after 3 days of culture was dose-dependent, exhibited a maximum response above 10 nM TCDD, and varied greatly among different individuals. However, the half maximal dose required for this induction was similar between individuals and comparable to that observed in the MCF-7 and HepG2 human cell lines. These observations indicate that CYP1B1 exhibits variable constitutive expression and is inducible in vitro by TCDD in human lymphocytes and that the magnitude of induction varies within the population. These data define the suitability of CYP1B1 for use as a mechanistically based biomarker in ongoing molecular epidemiological studies of human populations exposed to dioxins and related chemicals that bind the aromatic hydrocarbon receptor.
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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/4-hydroxyestradiol-17 beta,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 Enzyme System,
http://linkedlifedata.com/resource/pubmed/chemical/Environmental Pollutants,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Estrogens, Catechol,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrachlorodibenzodioxin,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP1B1
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1055-9965
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
139-46
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10067811-Adult,
pubmed-meshheading:10067811-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:10067811-Biological Markers,
pubmed-meshheading:10067811-Cytochrome P-450 Enzyme System,
pubmed-meshheading:10067811-Dose-Response Relationship, Drug,
pubmed-meshheading:10067811-Environmental Exposure,
pubmed-meshheading:10067811-Environmental Pollutants,
pubmed-meshheading:10067811-Estradiol,
pubmed-meshheading:10067811-Estrogens, Catechol,
pubmed-meshheading:10067811-Female,
pubmed-meshheading:10067811-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:10067811-Humans,
pubmed-meshheading:10067811-Leukocytes, Mononuclear,
pubmed-meshheading:10067811-Lymphocyte Activation,
pubmed-meshheading:10067811-Lymphocytes,
pubmed-meshheading:10067811-Male,
pubmed-meshheading:10067811-Middle Aged,
pubmed-meshheading:10067811-Mitogens,
pubmed-meshheading:10067811-Molecular Epidemiology,
pubmed-meshheading:10067811-RNA,
pubmed-meshheading:10067811-Tetrachlorodibenzodioxin,
pubmed-meshheading:10067811-Tumor Markers, Biological
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pubmed:year |
1999
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pubmed:articleTitle |
Quantitative analysis of constitutive and 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytochrome P450 1B1 expression in human lymphocytes.
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pubmed:affiliation |
Laboratory of Computational Biology and Risk Analysis, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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