Abstract
Previous studies have shown variability in naphthalene cytotoxicity, expression of CYP2F2 gene and protein, and naphthalene metabolism in random cycling female mice (NIH:Swiss). CYP2F2 metabolizes naphthalene to cytotoxic metabolites in lungs of mice. This study was designed to address the question: do hormonal changes associated with the estrous cycle alter metabolism of naphthalene in the lung? Adult virgin female mice were manipulated into defined stages of the reproductive cycle: estrus, proestrus, and noncycling. Cycling was confirmed by cytology on vaginal swabs. At specific cycle times, extrapulmonary (tracheal and bronchial) and intrapulmonary (bronchiolar) conducting airways were microdissected from the lung parenchyma and incubated with naphthalene, and the products of naphthalene metabolism were trapped and measured using high-performance liquid chromatography. Circulating estradiol levels were measured at necropsy using an enzyme-linked immunosorbent assay. CYP2F2 gene expression was determined by airway level using real-time reverse transcription-polymerase chain reaction and did not vary by estrous cycle stage in intrapulmonary airways but did in extrapulmonary airways. Metabolism of naphthalene varied significantly by estrous cycle stage with the highest level of total metabolism occurring in proestrus (when estrogen is lowest) in intrapulmonary airways. Total activity and metabolite profiles in both extrapulmonary and intrapulmonary airways were affected by cycle stage. We conclude that the hormonal patterns associated with different stages of the estrous cycle 1) alter metabolism of naphthalene in the lungs of mice and 2) alter naphthalene metabolism differentially in extrapulmonary versus intrapulmonary airways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1597-1602 |
| Number of pages | 6 |
| Journal | Drug Metabolism and Disposition |
| Volume | 33 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2005 |
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ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Estrous cycle alters naphthalene metabolism in female mouse airways. / Stelck, Rhonda L.; Baker, Gregory L.; Sutherland, Katherine M.; Van Winkle, Laura S.
In: Drug Metabolism and Disposition, Vol. 33, No. 11, 11.2005, p. 1597-1602.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Estrous cycle alters naphthalene metabolism in female mouse airways
AU - Stelck, Rhonda L.
AU - Baker, Gregory L.
AU - Sutherland, Katherine M.
AU - Van Winkle, Laura S.
PY - 2005/11
Y1 - 2005/11
N2 - Previous studies have shown variability in naphthalene cytotoxicity, expression of CYP2F2 gene and protein, and naphthalene metabolism in random cycling female mice (NIH:Swiss). CYP2F2 metabolizes naphthalene to cytotoxic metabolites in lungs of mice. This study was designed to address the question: do hormonal changes associated with the estrous cycle alter metabolism of naphthalene in the lung? Adult virgin female mice were manipulated into defined stages of the reproductive cycle: estrus, proestrus, and noncycling. Cycling was confirmed by cytology on vaginal swabs. At specific cycle times, extrapulmonary (tracheal and bronchial) and intrapulmonary (bronchiolar) conducting airways were microdissected from the lung parenchyma and incubated with naphthalene, and the products of naphthalene metabolism were trapped and measured using high-performance liquid chromatography. Circulating estradiol levels were measured at necropsy using an enzyme-linked immunosorbent assay. CYP2F2 gene expression was determined by airway level using real-time reverse transcription-polymerase chain reaction and did not vary by estrous cycle stage in intrapulmonary airways but did in extrapulmonary airways. Metabolism of naphthalene varied significantly by estrous cycle stage with the highest level of total metabolism occurring in proestrus (when estrogen is lowest) in intrapulmonary airways. Total activity and metabolite profiles in both extrapulmonary and intrapulmonary airways were affected by cycle stage. We conclude that the hormonal patterns associated with different stages of the estrous cycle 1) alter metabolism of naphthalene in the lungs of mice and 2) alter naphthalene metabolism differentially in extrapulmonary versus intrapulmonary airways.
AB - Previous studies have shown variability in naphthalene cytotoxicity, expression of CYP2F2 gene and protein, and naphthalene metabolism in random cycling female mice (NIH:Swiss). CYP2F2 metabolizes naphthalene to cytotoxic metabolites in lungs of mice. This study was designed to address the question: do hormonal changes associated with the estrous cycle alter metabolism of naphthalene in the lung? Adult virgin female mice were manipulated into defined stages of the reproductive cycle: estrus, proestrus, and noncycling. Cycling was confirmed by cytology on vaginal swabs. At specific cycle times, extrapulmonary (tracheal and bronchial) and intrapulmonary (bronchiolar) conducting airways were microdissected from the lung parenchyma and incubated with naphthalene, and the products of naphthalene metabolism were trapped and measured using high-performance liquid chromatography. Circulating estradiol levels were measured at necropsy using an enzyme-linked immunosorbent assay. CYP2F2 gene expression was determined by airway level using real-time reverse transcription-polymerase chain reaction and did not vary by estrous cycle stage in intrapulmonary airways but did in extrapulmonary airways. Metabolism of naphthalene varied significantly by estrous cycle stage with the highest level of total metabolism occurring in proestrus (when estrogen is lowest) in intrapulmonary airways. Total activity and metabolite profiles in both extrapulmonary and intrapulmonary airways were affected by cycle stage. We conclude that the hormonal patterns associated with different stages of the estrous cycle 1) alter metabolism of naphthalene in the lungs of mice and 2) alter naphthalene metabolism differentially in extrapulmonary versus intrapulmonary airways.
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UR - http://www.scopus.com/inward/citedby.url?scp=27544472069&partnerID=8YFLogxK
U2 - 10.1124/dmd.105.005124
DO - 10.1124/dmd.105.005124
M3 - Article
C2 - 16085760
AN - SCOPUS:27544472069
VL - 33
SP - 1597
EP - 1602
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
SN - 0090-9556
IS - 11
ER -