Document Detail


Estrogen metabolism within the lung and its modulation by tobacco smoke.
MedLine Citation:
PMID:  23276798     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although estrogen and the enzymes responsible for its metabolism have been detected within the lung, the ability of this tissue to metabolize estrogen has not been demonstrated previously. The goal of this study was to characterize the profile of estrogen metabolites within the murine lung and to determine the effect of tobacco smoke exposure on metabolite levels. Use of liquid chromatography-tandem mass spectrometry led to the detection of three estrogens (E1, E2 and E3) and five estrogen metabolites (2-OHE1, 4-OHE1, 4-OHE2, 2-OMeE1 and 2-OMeE2) within the perfused lung, with 4-OHE1 being the most abundant species. Levels of 4-OHEs, carcinogenic derivatives produced primarily by cytochrome P450 1B1 (Cyp1b1), were 2-fold higher in females than males. Deletion of Cyp1b1 in females led to a dramatic reduction (21-fold) in 4-OHEs, whereas levels of 2-OHE1 and the putative protective estrogen metabolite 2-OMeE2 were increased (2.4- and 5.0-fold, respectively) (P = 0.01). Similar quantitative differences in estrogen metabolite levels were observed between Cyp1b1 null and wild-type males. Exposure of female mice to tobacco smoke for 8 weeks (2h per day, 5 days per week) increased the levels of 4-OHE1 (4-fold) and 2-OHE2 (2-fold) within the lung while reducing the total concentration of 2-OMeEs to 70% of those of unexposed controls. These data suggest that tobacco smoke accelerates the production of 4-OHEs within the lung; carcinogenic metabolites that could potentially contribute to lung tumor development. Thus, inhibition of CYP1B1 may represent a promising strategy for the prevention and treatment of lung cancer.
Authors:
Jing Peng; Xia Xu; Brian E Mace; Lisa A Vanderveer; Laura R Workman; Michael J Slifker; Patrick M Sullivan; Timothy D Veenstra; Margie L Clapper
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-31
Journal Detail:
Title:  Carcinogenesis     Volume:  34     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-06-17     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  909-15     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Aryl Hydrocarbon Hydroxylases / genetics,  metabolism*
Catechol O-Methyltransferase / metabolism
Estrogens / metabolism*
Female
Genotype
Lung / metabolism*
Lung Neoplasms / metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Sex Factors
Smoke*
Tobacco*
Grant Support
ID/Acronym/Agency:
CA006927/CA/NCI NIH HHS; CA167721/CA/NCI NIH HHS; R03 CA167721/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 0/Smoke; EC 1.14.14.1/Aryl Hydrocarbon Hydroxylases; EC 1.14.14.1/cytochrome P-450 CYP1B1; EC 2.1.1.6/Catechol O-Methyltransferase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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