Effect of smoke and gender on bronchiolar injury and repair

Institution:	University of California, Davis
Investigator(s):	Laura Van Winkle, Ph.D.
Award Cycle:	2002 (Cycle 11)	Grant #: 11RT-0258	Award: $413,288
Subject Area:	Pulmonary Disease
Award Type:	Research Project Awards

Abstracts

Initial Award Abstract

Environmental tobacco smoke (ETS) is a substantial public health hazard because of the large number of smokers and the widespread presence of ETS that can lead to involuntary exposure of nonsmokers. ETS exposure is causally associated with lung cancer in both adult men and women. However, important differences exist in susceptibility to lung cancer between men and women. The risk for all major lung cancer types is higher in women than in men at every level of exposure to tobacco smoke. Recent research has shown that women express certain genes at increased levels in response to tobacco smoke. These changes are not seen in men exposed to tobacco smoke. While these changes suggest that there are genetic reasons for the differences in lung cancer risk between men and women, there have been few studies that define the biologic basis for these differences.

The proposed research will focus on the cellular changes that occur in mice exposed to tobacco smoke and will determine if these changes are different in female mice compared to male mice. Subtle effects such as cellular changes in response to ETS in males and females have not been thoroughly investigated. Furthermore, because these subtle changes may be very focal within the lung the experimental approach must use methods that are also site-specific and that can evaluate cellular changes in focal lung regions. Our laboratory frequently uses and develops new site-specific methods such as these and will apply them in the proposed studies. Preliminary data from our laboratory suggest that female mice are more sensitive to an air pollutant, naphthalene, that is found in both cigarette smoke and car exhaust. We feel that coexposure to tobacco smoke and excess naphthalene in air pollution may result in an accentuated effect (such as cell changes that lead to cancer or chronic bronchitis) in female animals. Our hypothesis in the proposed studies is that female mice will have increased lung injury compared to males. We will try to determine the mechanism for the cellular changes.

This research has potential impact for women who smoke or are exposed to ETS and who live in urban areas with high levels of air pollution. We expect these studies will benefit the general population by defining the mechanisms that make women more susceptible. Once this mechanism has been defined strategies can be devised that will afford sensitive populations some protection. These studies are highly relevant to TRDRP research priorities regarding tobacco smoke exposure in a sensitive population, women.

Publications

Detection of viral infection in the respiratory tract of virus antibody free mice: advantages of high-resolution imaging for respiratory toxicology.
Periodical: Toxicology and Applied Pharmacology			Index Medicus:
Authors: Phimister AJ, Day KC, Gunderson AD, Wong VU, Lawson GW, Fanucchi MV, Van Winkle LS, et al				ART
Yr: 2003	Vol: 190	Nbr:	Abs:	Pg: 286-293

Mechanisms intrinsic to Clara cells of mice produce tolerance to repeated inhalation exposures of the bioactivated cytotoxicant naphthalene.
Periodical: Toxicological Sciences			Index Medicus:
Authors: West JAA, Van Winkle LS, Morin D, Fleschner CA, Forman HJ, Buckpitt AR, Plopper CG				ART
Yr: 2003	Vol: 75	Nbr:	Abs:	Pg: 161-8

Quantitative comparison of epithelial injury and repair responses to naphthalene alone and incombination with sidestream tobacco smoke.
Periodical: FASEB Journal			Index Medicus:
Authors: Van Winkle LS, Brown CD, Stelck RL, Shimizu JA, Hyde DM, Evans MJ, Plopper CG				ABS
Yr: 2003	Vol: 17	Nbr: 5	Abs:	Pg: A1377

Sex-specific induction of pulmonary glutathione s-transferase (GST) and CYP2F2 after chronic pre and postnatal exposure to sidestream tobacco smoke (TS).
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle LS, Baker GL, Brown CD, Stelck RL, Shimizu JA, Evans MJ, Plopper CG				ABS
Yr: 2003	Vol: 167	Nbr: 7	Abs:	Pg: A972

Determination of site-specific airway gene expression utilizing a novel technique of in situ RNA preservation.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Baker GL, Schultz M, Fanucchi MV, Buckpitt AR, Plopper CG				ABS
Yr: 2003	Vol: 167	Nbr: 7	Abs:	Pg: A336

Male/female differences in pulmonary epithelial responses to environmental tobacco smoke (ETS)
Periodical: TRDRP Annual Report to the State of California Legislature			Index Medicus:
Authors: Van Winkle LS, Stelck RL, Shimizu JA, Brown CD, Baker GL				ABS
Yr: 2003	Vol:	Nbr:	Abs: t57	Pg: 51

Estrous cycle and estrogen receptor expression in the female mouse lung.
Periodical: Molecular Biology of the Cell			Index Medicus:
Authors: Van Winkle LS, Baker GL, Stelck RL, Shimizu JA, Brown CD, Plopper CG				ABS
Yr: 2003	Vol: 14	Nbr: S	Abs: 657	Pg: 119a

Estrous cycle alters pulmonary metabolism of naphthalene (NA)
Periodical: Toxicologist			Index Medicus:
Authors: Van Winkle LS, Baker GL, Stelck RL, Brown CD, Plopper CG, Buckpitt AR				ABS
Yr: 2004	Vol: 78	Nbr: S-1	Abs: 705	Pg: 145

Differential exppression of trefoil factors 1 and 3 following airway epithelial cell injury.
Periodical: Toxicologist			Index Medicus:
Authors: Baker GL, Van Winkle LS, Fanucchi MV, Kim DC, Ploppper CG				ABS
Yr: 2004	Vol: 78	Nbr: S-1	Abs: 1395	Pg: 287

Assessing gene expression in lung subcompartments utilizing in situ RNA preservation.
Periodical: Toxicological Sciences			Index Medicus:
Authors: Baker GL, Shultz MA, Fanucchi MV, Morin DM, Buckpitt AR, Plopper CG				ART
Yr: 2004	Vol: 77	Nbr: 1	Abs:	Pg: 135-41

Impaired recovery from naphthalene-induced bronchiolar epithelial injury in mice exposed to aged and diluted sidesteam cigarette smoke.
Periodical: Toxicology Letters			Index Medicus:
Authors: Van Winkle LS, Brown CD, Shimizu JA, Gunderson AD, Evans MJ, Plopper CG				ART
Yr: 2004	Vol: 154	Nbr: 1-2	Abs:	Pg: 1 - 9

Consequences of abrupt glutathione depletion in murine clara cells: ultrastructural and biochemical investigations into the role of glutathione loss in naphthalene cytotoxcity.
Periodical: JPET			Index Medicus:
Authors: Phimister AL, Williams KJ, Van Winkle LS, Plopper CG				ART
Yr: 2005	Vol: 314	Nbr: 2	Abs:	Pg: 506 - 513

Estrous cycle alters naphthalene metabolism in female mouse airways.
Periodical: Drug Metabolism and Disposition			Index Medicus:
Authors: Stelck RL, Baker GL, Sutherland KM, Van Winkle LS				ART
Yr: 2005	Vol: 33	Nbr:	Abs:	Pg: 1597 - 1602

Quantitation of airway specific gene expression of endothelin-1 and it's receptors during injury and repair in the adult mouse lung.
Periodical: Toxicologist			Index Medicus:
Authors: Baker GL, Sutherland KT, Brown CD, Plopper CG, Van Winkle LS				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg:

Effect of tobacco smoke on the expression of genes involved in naphthalene (NA) metabolism.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle L, Sutherland K, Stelck R, Brown C, Baker G				ART
Yr: 2005	Vol: 2	Nbr:	Abs:	Pg: A224

Sensitivity to naphthalene (NA) vapor varies by sex and estrous cycle stage.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle L, Stelck K, Sutherland K, Brown C, Shimizu J, Baker G				ART
Yr: 2005	Vol: 2	Nbr:	Abs:	Pg: A168

Peroxiredoxin-6 is decreased in both male and female adult mouse airways by exposure to tobacco smoke.
Periodical: Society of Toxicology			Index Medicus:
Authors: Van Winkle LS, Baker GL, Sutherland KM				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg:

Airway proteomics in the mouse lung: a comparison of two approaches and their ability to detect sex differences in airway proteins.
Periodical: Society of Toxicology			Index Medicus:
Authors: Sutherland KM, Isbell MA, Van Winkle LS				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg:

Detection of viral infection in the respiratory tract of virus antibody free mice: advantages of high-resolution imaging for respiratory toxicology.
Periodical: Toxicology and Applied Pharmacology			Index Medicus:
Authors: Phimister AJ, Day KC, Gunderson AD, Wong VU, Lawson GW, Fanucchi MV, Van Winkle LS, et al				ART
Yr: 2003	Vol: 190	Nbr:	Abs:	Pg: 286-293

Mechanisms intrinsic to Clara cells of mice produce tolerance to repeated inhalation exposures of the bioactivated cytotoxicant naphthalene.
Periodical: Toxicological Sciences			Index Medicus:
Authors: West JAA, Van Winkle LS, Morin D, Fleschner CA, Forman HJ, Buckpitt AR, Plopper CG				ART
Yr: 2003	Vol: 75	Nbr:	Abs:	Pg: 161-8

Quantitative comparison of epithelial injury and repair responses to naphthalene alone and incombination with sidestream tobacco smoke.
Periodical: FASEB Journal			Index Medicus:
Authors: Van Winkle LS, Brown CD, Stelck RL, Shimizu JA, Hyde DM, Evans MJ, Plopper CG				ABS
Yr: 2003	Vol: 17	Nbr: 5	Abs:	Pg: A1377

Sex-specific induction of pulmonary glutathione s-transferase (GST) and CYP2F2 after chronic pre and postnatal exposure to sidestream tobacco smoke (TS).
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle LS, Baker GL, Brown CD, Stelck RL, Shimizu JA, Evans MJ, Plopper CG				ABS
Yr: 2003	Vol: 167	Nbr: 7	Abs:	Pg: A972

Determination of site-specific airway gene expression utilizing a novel technique of in situ RNA preservation.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Baker GL, Schultz M, Fanucchi MV, Buckpitt AR, Plopper CG				ABS
Yr: 2003	Vol: 167	Nbr: 7	Abs:	Pg: A336

Male/female differences in pulmonary epithelial responses to environmental tobacco smoke (ETS)
Periodical: TRDRP Annual Report to the State of California Legislature			Index Medicus:
Authors: Van Winkle LS, Stelck RL, Shimizu JA, Brown CD, Baker GL				ABS
Yr: 2003	Vol:	Nbr:	Abs: t57	Pg: 51

Estrous cycle and estrogen receptor expression in the female mouse lung.
Periodical: Molecular Biology of the Cell			Index Medicus:
Authors: Van Winkle LS, Baker GL, Stelck RL, Shimizu JA, Brown CD, Plopper CG				ABS
Yr: 2003	Vol: 14	Nbr: S	Abs: 657	Pg: 119a

Estrous cycle alters pulmonary metabolism of naphthalene (NA)
Periodical: Toxicologist			Index Medicus:
Authors: Van Winkle LS, Baker GL, Stelck RL, Brown CD, Plopper CG, Buckpitt AR				ABS
Yr: 2004	Vol: 78	Nbr: S-1	Abs: 705	Pg: 145

Differential exppression of trefoil factors 1 and 3 following airway epithelial cell injury.
Periodical: Toxicologist			Index Medicus:
Authors: Baker GL, Van Winkle LS, Fanucchi MV, Kim DC, Ploppper CG				ABS
Yr: 2004	Vol: 78	Nbr: S-1	Abs: 1395	Pg: 287

Assessing gene expression in lung subcompartments utilizing in situ RNA preservation.
Periodical: Toxicological Sciences			Index Medicus:
Authors: Baker GL, Shultz MA, Fanucchi MV, Morin DM, Buckpitt AR, Plopper CG				ART
Yr: 2004	Vol: 77	Nbr: 1	Abs:	Pg: 135-41

Impaired recovery from naphthalene-induced bronchiolar epithelial injury in mice exposed to aged and diluted sidesteam cigarette smoke.
Periodical: Toxicology Letters			Index Medicus:
Authors: Van Winkle LS, Brown CD, Shimizu JA, Gunderson AD, Evans MJ, Plopper CG				ART
Yr: 2004	Vol: 154	Nbr: 1-2	Abs:	Pg: 1 - 9

Consequences of abrupt glutathione depletion in murine clara cells: ultrastructural and biochemical investigations into the role of glutathione loss in naphthalene cytotoxcity.
Periodical: JPET			Index Medicus:
Authors: Phimister AL, Williams KJ, Van Winkle LS, Plopper CG				ART
Yr: 2005	Vol: 314	Nbr: 2	Abs:	Pg: 506 - 513

Estrous cycle alters naphthalene metabolism in female mouse airways.
Periodical: Drug Metabolism and Disposition			Index Medicus:
Authors: Stelck RL, Baker GL, Sutherland KM, Van Winkle LS				ART
Yr: 2005	Vol: 33	Nbr:	Abs:	Pg: 1597 - 1602

Quantitation of airway specific gene expression of endothelin-1 and it's receptors during injury and repair in the adult mouse lung.
Periodical: Toxicologist			Index Medicus:
Authors: Baker GL, Sutherland KT, Brown CD, Plopper CG, Van Winkle LS				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg:

Effect of tobacco smoke on the expression of genes involved in naphthalene (NA) metabolism.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle L, Sutherland K, Stelck R, Brown C, Baker G				ART
Yr: 2005	Vol: 2	Nbr:	Abs:	Pg: A224

Sensitivity to naphthalene (NA) vapor varies by sex and estrous cycle stage.
Periodical: American Journal of Respiratory and Critical Care Medicine			Index Medicus:
Authors: Van Winkle L, Stelck K, Sutherland K, Brown C, Shimizu J, Baker G				ART
Yr: 2005	Vol: 2	Nbr:	Abs:	Pg: A168

Peroxiredoxin-6 is decreased in both male and female adult mouse airways by exposure to tobacco smoke.
Periodical: Society of Toxicology			Index Medicus:
Authors: Van Winkle LS, Baker GL, Sutherland KM				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg:

Airway proteomics in the mouse lung: a comparison of two approaches and their ability to detect sex differences in airway proteins.
Periodical: Society of Toxicology			Index Medicus:
Authors: Sutherland KM, Isbell MA, Van Winkle LS				ART
Yr: 0	Vol:	Nbr:	Abs:	Pg: