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ETS Effects on airway development in the primate lung

Institution: University of California, Davis
Investigator(s): Kent Pinkerton, Ph.D.
Award Cycle: 1998 (Cycle 7) Grant #: 7RT-0118 Award: $483,652
Subject Area: General Biomedical Science
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Environmental tobacco smoke (ETS) is defined as the combination of sidestream smoke released from the burning end of a cigarette and that portion of mainstream smoke exhaled by smokers. Health effects associated with exposure to ETS have been clearly demonstrated, but still remain somewhat controversial. In 1993 the U.S. Environmental Protection Agency declared environmental tobacco smoke (ETS) to be a human carcinogen that kills approximately 3,000 nonsmokers a year. Young children are also affected by ETS exposure with increases in the incidence of pneumonia, bronchitis and middle ear infection. For children with asthma, ETS exposure increases the severity and frequency of asthmatic attacks. However, the cause(s) for greater and more adverse health risks associated with ETS exposure in children compared with adults is (are) unknown. We propose to study in our laboratory the effects of exposure to ETS on the maturation and function of the lung airways during fetal and early postnatal development in monkeys. This species is ideal to study due to its high degree of similarity in development and anatomy to that of humans. We have found that exposure to ETS during the fetal and early postnatal periods is associated with a significant increase in airway narrowing, similar to that seen in asthmatic children. Also associated with these hyperactive airways is a dramatic increase in pulmonary neuroendocrine cells (PNECs), rare epithelial cells lining the lung airways. The function of these cells is unknown; however, they are thought to be important in the lungs’ response to substances that are inhaled; it is our hypothesis that PNECs may be directly responsible for the increased airway reactivity noted in the lungs of asthmatic patients. We propose to test this hypothesis in monkeys using ETS exposures during critical periods of lung growth and development. An important observation from our laboratory has been that rodents exposed to ETS in utero (via the mother) and then directly exposed to ETS after birth, have lungs that are markedly hyperresponsive (i.e., overly reactive to inhaled compounds) compared with rodents exposed only to filtered air. To better extrapolate these findings to humans, we will repeat these studies using monkeys. The changes previously observed in rodents are highly analogous to anatomical changes that precede the development of childhood asthma in humans. Extension of these studies in monkeys affords us the opportunity to examine critical periods of lung development when exposure to ETS may result in increased airway hyperresponsiveness and whether changes in airway PNEC number and/or function might be responsible for these observed changes.
Publications

Perinatal exposure to aged and diluted sidestream cigarette smoke produces airway hyperresponsiveness in older rats
Periodical: Toxicology and Applied Pharmacology Index Medicus:
Authors: Joad JP, Bric JM, Peake JL, Pinkerton KE ART
Yr: 1998 Vol: 155 Nbr: Abs: Pg: 253-260

Site-selective differences in cytochrome P450 isoform activities. Comparison of expression in rat and rhesus monkey lung and induction in rats
Periodical: Drug Metabolism and Disposition Index Medicus:
Authors: Lee C, Watt KC, Chang AM, Plopper CG, Buckpitt AR, Pinkerton KE ART
Yr: 1998 Vol: 26 Nbr: Abs: Pg: 396-400

Species variability in the cellular and metabolic characteristics of the mammalian lung
Periodical: Toxicologist Index Medicus:
Authors: Plopper CG, Evans MJ, Pinkerton KE, Buckpitt AR ABS
Yr: 1998 Vol: 42 Nbr: 1-S Abs: Pg: 570

Comparative biology of the lower respiratory tract: relevance to environmental air pollutants
Periodical: Toxicologist Index Medicus:
Authors: Pinkerton KE, Hyde DM, Evans MJ, Plopper CG ABS
Yr: 1998 Vol: 42 Nbr: 1-S Abs: Pg: 573

Effects of in utero & postnatal exposure to environmental tobacco smoke on developmental expression of pulmonary cytochrome P450 genes
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Lee C, Royce FH, Pinkerton KE ABS
Yr: 1998 Vol: 157 Nbr: 3 Abs: Pg: A544

Environmental tobacco smoke and perinatal airway remodeling
Periodical: Toxicologist Index Medicus:
Authors: Pinkerton KE, Avadhanam KP, Bric J, Kott K, Joad J ABS
Yr: 1999 Vol: 48 Nbr: 1-S Abs: Pg: 783

Perinatal exposure to environmental tobacco smoke alters cell signalling in a primate model: autonomic receptors and the control of adenylyl cyclase acitvity in heart and lung
Periodical: Developmental Brain Research Index Medicus:
Authors: Slotkin TA, Pinkerton KE, Seidler FJ ART
Yr: 2000 Vol: 124 Nbr: Abs: Pg: 53-58

Prior exposure to aged and diluted sidestream cigarette smoke impairs bronchiolar injury and repair
Periodical: Toxicological Sciences Index Medicus:
Authors: Van Winkle LS, Evans MJ, Brown CD, Willits NH, Pinkerton KE, Plopper CG ART
Yr: 2001 Vol: 60 Nbr: Abs: Pg: 152-164

Perinatal exposure to environmental tobacco smoke induces adenylyl cyclase and alters receptor-mediated cell signaling in brain and heart of neonatal rats
Periodical: Brain Research Index Medicus:
Authors: Slotkin TA, Pinkerton KE, Garofolo MC, Auman JT, McCook EC, Seidler FJ ART
Yr: 2001 Vol: 898 Nbr: Abs: Pg: 73-81

Environmental tobacco smoke (ETS) increases ozone-induced lung injury in a dose-dependent manner
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Yu M, Witschi HP, Pinkerton KE ABS
Yr: 2000 Vol: 161 Nbr: 3 Abs: A174 Pg:

Exposure to environmental tobacco smoke (ETS) enhances the sensitivity of the lungs to ozone-induced injury
Periodical: Toxicologist Index Medicus:
Authors: Pinkerton KE, Yu M, Witschi HP ABS
Yr: 2000 Vol: 54 Nbr: 1 Abs: 1147 Pg:

Gender differences in environmental tobacco smoke enhancement of the allergic response
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: Gershwin LJ, Seymour BWP, Pinkerton KE, Friebertshauser KE ABS
Yr: 2000 Vol: Nbr: Abs: 24 Pg:

Sidestream smoke exposure iimpairs lung repair from injury
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Van Winkle LS, Evans MJ, Brown, et al ABS
Yr: 2000 Vol: 161 Nbr: 3 Abs: 174 Pg:

Environmental tobacco smoke (ETS) significantly alters perinatal lung development in non-human primates
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: Pinkerton KE, Yu M, Zhong C, et al ABS
Yr: 2000 Vol: Nbr: Abs: Pg: 24

Environmental tobacco smoke and depletion of gonadal steroids exacerbates atherosclerosis in female LDL receptor-deficient mice
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: Ruecker DR, Pinkerton KE, Banka CL ABS
Yr: 2000 Vol: Nbr: Abs: Pg: 62

Environmental tobacco smoke exposure increases permeability and glycoxidative damage to the artery wall
Periodical: Proceedings of the TRDRP Annual Investigator's Meeting Index Medicus:
Authors: McDonald M, Pinkerton KE, Rutledge JC ABS
Yr: 2000 Vol: Nbr: Abs: Pg: 65

Environmental tobacco smoke induces inflammation and apoptosis in the lung of spontaneously hypersensitive rats
Periodical: Toxicologist Index Medicus:
Authors: Smith KR, Yu B, Kodavani UP, Pinkerton KE ABS
Yr: 2001 Vol: 60 Nbr: 1 Abs: 81 Pg:

Perinatal exposure to environmental tobacco smoke (ETS) induces brain-derived neurotrophic factor (BDNF) and th2 cytokines in young rhesus monkeys
Periodical: Toxicologist Index Medicus:
Authors: Yu M, Pinkerton KE ABS
Yr: 2001 Vol: 60 Nbr: 1 Abs: 197 Pg:

Perinatal exposure to environmental tobacco smoke (ETS) induces regio-selective cytochrome P450 and oxidative stress in the lungs of neonatal monkeys
Periodical: Toxicologist Index Medicus:
Authors: Zhong CY, Zhou YM, Chang AM, Buckpitt AR, Pinkerton KE ABS
Yr: 2001 Vol: 60 Nbr: 1 Abs: Pg: 197-198

Critical windows of neonatal sensitivity of the respiratory tract to toxicants
Periodical: Toxicologist Index Medicus:
Authors: Pinkerton KE, Plopper CG ABS
Yr: 2001 Vol: 60 Nbr: 1 Abs: Pg: 264

Perinatal effects of environmental tobacco smoke on the lungs
Periodical: Toxicologist Index Medicus:
Authors: Pinkerton KE, Avadhaman KP, Joad JP ABS
Yr: 2001 Vol: 60 Nbr: 1 Abs: Pg: 264

The role of interleukin (IL) in environmental tobacco smoke (ETS) induced enhancement of ozone (O3) lung injury
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Yu M, Zheng X, Witschi HP, Pinkerton KE ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 176

Environmental air pollutants alter pulmonary neurotrophin levels: the role of interleukin (IL)-6
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Yu M, Pinkerton KE ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 176

Chemokine expression and accumulation of dendritic cells following exposure to environmental tobacco smoke
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Miller LA, Gurley E, Wang B, Gershwin LJ, Pinkerton KE ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: 177 Pg:

Site-specific alteration of pulmonary xenobiotics metabolizing enzymes in infant monkeys perinatally exposed to environmental tobacco smoke (ETS)
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Zhong CY, Zhou YM, Chang AM, Buckpitt AR, Pinkerton KE ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 177

Gender differences in environmental tobacco smoke enhancement of the allergic response
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Seymour BWP, Friebertshauser KE, Pinkerton KE, Gershwin L ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 262

Impaired bronchiolar epithelial repair after environmental tobacco smoke (ETS) exposure
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: van Winkle LS, Evans MJ, Brown CD, Shimizu JA, Pinkerton KE, Plopper CG ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 363

Environmental tobacco smoke (ETS) alters tracheal innervation and epithelial cell composition in non-human primate infants
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Pinkerton KE, Peake JL, Joad JP ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 363

Videomicrometry of responsiveness of central and peripheral airways in rats and monkeys
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Kott KS, Pinkerton KE, Bric JM, Avadhanam K, Plopper CG, Joad JP ABS
Yr: 2001 Vol: 163 Nbr: 5 Abs: Pg: 925

Alteration of pulmonary neuroendocrine cells during epithelial repair of naphthalene-induced airway injury
Periodical: American Journal of Pathology Index Medicus:
Authors: Peake JL, Reynolds SD, Stripp BR, Stephens KE, Pinkerton KE ART
Yr: 2000 Vol: 156 Nbr: Abs: Pg: 279-286

Effect of in utero and postnatal exposure to environmental tobacco smoke on the developmental expression of pulmonary cytochrome P450 monooxygenases
Periodical: Journal of Biochemical and Molecular Toxicology Index Medicus:
Authors: Lee CZ, Royce FH, Denison MS, Pinkerton KE ART
Yr: 2000 Vol: 14 Nbr: Abs: Pg: 121-130

The mammalian respiratory system and critical windows of exposure for children's health
Periodical: Environmental Health Perspectives Index Medicus:
Authors: Pinkerton KE, Joad JP ART
Yr: 2000 Vol: 108 Nbr: 3 Abs: Pg: 457-462

Effects of maternal exposure to beta-naphthoflavone (BNF) on amniotic fluid volume and fetal lung development
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Albuquerque CA, Royce F, Stephens K, Gilbert W, Pinkerton KE ABS
Yr: 1999 Vol: 159 Nbr: 3 Abs: A669 Pg:

Effects of environmental tobacco smoke (ETS) on perinatal lung development in rhesus monkeys
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Pinkerton KE, Joad JP, Yu M, et al ABS
Yr: 2000 Vol: 161 Nbr: 3 Abs: A174 Pg:

Comparison of airway reactivity and epithelium the same airway slices of allergic primates
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Joad JP, Kott KS, Bric JM, Murphy K, Pinkerton KE ABS
Yr: 2000 Vol: 161 Nbr: 3 Abs: A274 Pg:

A receptor-mediated mechanism of nicotine toxicity in oral keratinocytes.
Periodical: Laboratory Investigations Index Medicus:
Authors: Arredondo J, Nguyen VT, Chernyavsky AL, et al ART
Yr: 2001 Vol: 81 Nbr: 12 Abs: Pg: 1653-1668

Short-term exposure to aged and diluted sidestream cigarette smoke enhances ozone-induced lung injury in B6C3F1 mice.
Periodical: Toxicological Sciences Index Medicus:
Authors: Yu M, Pinkerton KE, and Witschi H ABS
Yr: 2002 Vol: 65 Nbr: 1 Abs: Pg: 99 - 106

Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular issues.
Periodical: Circulation Index Medicus:
Authors: Knight-Lozano CA, Young CG, Burow DL, et al ART
Yr: 2002 Vol: 105 Nbr: 7 Abs: Pg: 849 - 854

Perinatal exposure to environmental tobacco smoke upregulates nicotinic cholinergic receptors in monkey brain.
Periodical: Brain Research. Developmental Brain Research Index Medicus:
Authors: Slotkin TA, Pinkerton KE, Auman JT, Ziao D, and Seidler JF ART
Yr: 2002 Vol: 133 Nbr: 2 Abs: Pg: 175 - 179

The role of interleukin-6 in pulmonary inflammation and injury induced by exposure to environmental air pollutants.
Periodical: Toxicological Sciences Index Medicus:
Authors: Yu M, Zheng X, Witschi H, and Pinkerton KE ART
Yr: 2002 Vol: 68 Nbr: Abs: Pg: 488 - 497

Gender differences in the allergic response of mice neonatally exposed to environmental tobacco smoke.
Periodical: Developmental Immunology Index Medicus:
Authors: Seymour BWP, Friebertshauser KE, et. al ART
Yr: 2002 Vol: 9 Nbr: 1 Abs: Pg: 47 - 54

Inhibition of tobacco smoke-induced lung inflammation by a catalytic antioxidant.
Periodical: Free Radical Biology and Medicine Index Medicus:
Authors: Smith KR, Uyeminami DL, et. al ART
Yr: 2002 Vol: 33 Nbr: 8 Abs: Pg: 1106 - 1114

Reactive cabronyls from tobacco smoke increase arterial endothelial layer injury
Periodical: American Journal of Physiology, Heart and Circulatory Physiology Index Medicus:
Authors: Mullick AE, McDonald JM, et. al ART
Yr: 2002 Vol: 283 Nbr: Abs: Pg: H591-H597

Exposure to sidestream cigarette smoke alters bronchiolar epithelial cell cytochrome P450 isozyme differentiation in the postnatal nonhuman primate.
Periodical: American Journal of Respiratory and Critical Care Medicine Index Medicus:
Authors: Shafii MA, et. al ABS
Yr: 2002 Vol: 165 Nbr: 8 Abs: A680 Pg: