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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0014912,
umls-concept:C0017262,
umls-concept:C0024109,
umls-concept:C0035647,
umls-concept:C0086418,
umls-concept:C0185117,
umls-concept:C0332282,
umls-concept:C0387583,
umls-concept:C0442805,
umls-concept:C1627358,
umls-concept:C1704675,
umls-concept:C2349975,
umls-concept:C2911684
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pubmed:issue |
7
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pubmed:dateCreated |
2007-7-12
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pubmed:abstractText |
Animal studies demonstrated that females are more susceptible than males to benzo[a]pyrene (BaP)-induced toxicities, including lung carcinogenesis. Elevation of cyclooxygenase-2 (COX-2) expression has been shown to increase the risk of cancer development. BaP induces COX-2 expression, and an interaction between BaP and estrogen in relation to COX-2 expression is suspected. In the present study, 10 muM BaP alone only slightly increased COX-2 mRNA expression and 10 nM 17-beta estradiol (E(2)) alone slightly increased prostaglandin E2 (PGE2) secretion in human bronchial epithelial cells. However, co-treatment with BaP and E(2) potentiated COX-2 mRNA expression and significantly elevated PGE2 secretion. Utilizing specific inhibitors and reporter assays, we further investigated the potentiation mechanisms of E(2) on BaP-induced COX-2 expression. First, E(2) activated estrogen receptor to increase PGE2 secretion, which directly increased COX-2 expression. Second, E(2) potentiated BaP-induced nuclear factor-kappaB (NF-kappaB) activation, which regulates COX-2 expression. Third, although the aryl hydrocarbon receptor (AhR) did not play a role in BaP-induced COX-2 expression, the potentiation effect of E(2) itself was AhR dependent. We further demonstrated that BaP induced the production of genotoxic E(2) metabolites (2- and 4-hydroxyestradiols) via AhR-up-regulated cytochromes P450 1A1 and 1B1. These metabolites could directly activate NF-kappaB to further promote COX-2 mRNA expression in human lung epithelial cells. These findings were further supported by increased PGE2 secretion in rat lung slice cultures. Our findings that the BaP-E(2) interaction enhanced COX-2 expression and hydroxyestradiol accumulation in the media of cultivated lung cells and tissues provide the needed scientific basis for higher risk of BaP-associated lung cancer in females.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-hydroxyestradiol,
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxyestradiol-17 beta,
http://linkedlifedata.com/resource/pubmed/chemical/Air Pollutants,
http://linkedlifedata.com/resource/pubmed/chemical/Aryl Hydrocarbon Hydroxylases,
http://linkedlifedata.com/resource/pubmed/chemical/Benzo(a)pyrene,
http://linkedlifedata.com/resource/pubmed/chemical/Carcinogens, Environmental,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome P-450 CYP1A1,
http://linkedlifedata.com/resource/pubmed/chemical/Dinoprostone,
http://linkedlifedata.com/resource/pubmed/chemical/Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/PTGS2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Estradiol,
http://linkedlifedata.com/resource/pubmed/chemical/cytochrome P-450 CYP1B1,
http://linkedlifedata.com/resource/pubmed/chemical/fulvestrant
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0143-3334
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1606-12
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pubmed:meshHeading |
pubmed-meshheading:17272310-Air Pollutants,
pubmed-meshheading:17272310-Animals,
pubmed-meshheading:17272310-Aryl Hydrocarbon Hydroxylases,
pubmed-meshheading:17272310-Benzo(a)pyrene,
pubmed-meshheading:17272310-Bronchi,
pubmed-meshheading:17272310-Carcinogens, Environmental,
pubmed-meshheading:17272310-Cells, Cultured,
pubmed-meshheading:17272310-Cyclooxygenase 2,
pubmed-meshheading:17272310-Cytochrome P-450 CYP1A1,
pubmed-meshheading:17272310-Dinoprostone,
pubmed-meshheading:17272310-Drug Synergism,
pubmed-meshheading:17272310-Enzyme Activation,
pubmed-meshheading:17272310-Epithelial Cells,
pubmed-meshheading:17272310-Estradiol,
pubmed-meshheading:17272310-Humans,
pubmed-meshheading:17272310-Lung,
pubmed-meshheading:17272310-Male,
pubmed-meshheading:17272310-Membrane Proteins,
pubmed-meshheading:17272310-NF-kappa B,
pubmed-meshheading:17272310-Rats,
pubmed-meshheading:17272310-Rats, Sprague-Dawley,
pubmed-meshheading:17272310-Receptors, Estradiol,
pubmed-meshheading:17272310-Up-Regulation
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pubmed:year |
2007
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pubmed:articleTitle |
Increase of carcinogenic risk via enhancement of cyclooxygenase-2 expression and hydroxyestradiol accumulation in human lung cells as a result of interaction between BaP and 17-beta estradiol.
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pubmed:affiliation |
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, No. 35, Keyan Road, Zhunan Town, Miaoli County 350, Taiwan, Republic of China.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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