Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats

Renee Paige, Viviana Wong, Charles Plopper

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Nonciliated ('Clara') cells of terminal bronchioles are one of the principal targets of bioactivated pulmonary toxicants. However, we have recently observed cytotoxicity in proximal tracheobronchial airways with high doses of naphthalene. To test if this was true for other xenobiotics, 1- nitronaphthalene (25, 50, 100, or 150 mg/kg) was injected ip into male Sprague-Dawley rats and cytotoxicity characterized 24 hr later by high- resolution histopathology along a defined airway path extending from the trachea to the terminal bronchioles. At 25 mg/kg, only nonciliated cells in minor daughter airways were swollen and necrotic. At 50 mg/kg there was near complete loss of nonciliated cells in most bronchioles, minor daughter airways, and tracheas. Marked damage to ciliated cells was observed at doses of 100 and 150 mg/kg. Denudation of the basement membrane was common in the trachea. We conclude for 1-nitronaphthalene cytotoxicity in the lung that: (1) nonciliated cells of the distal bronchioles are not the only target, (2) the threshold for injury in nonciliated cells is lower than that for ciliated cells, (3) the response is airway selective, (4) the response is dose- related.

Original languageEnglish (US)
Pages (from-to)224-233
Number of pages10
JournalToxicology and Applied Pharmacology
Volume147
Issue number2
DOIs
StatePublished - Jan 1 1997

Fingerprint

Toxicity
Rats
Bronchioles
Cytotoxicity
Trachea
Xenobiotics
Lung
1-nitronaphthalene
Basement Membrane
Sprague Dawley Rats
Wounds and Injuries

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats. / Paige, Renee; Wong, Viviana; Plopper, Charles.

In: Toxicology and Applied Pharmacology, Vol. 147, No. 2, 01.01.1997, p. 224-233.

Research output: Contribution to journalArticle

@article{d68e1ec59b6b473ab21adf3a286b4b53,
title = "Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats",
abstract = "Nonciliated ('Clara') cells of terminal bronchioles are one of the principal targets of bioactivated pulmonary toxicants. However, we have recently observed cytotoxicity in proximal tracheobronchial airways with high doses of naphthalene. To test if this was true for other xenobiotics, 1- nitronaphthalene (25, 50, 100, or 150 mg/kg) was injected ip into male Sprague-Dawley rats and cytotoxicity characterized 24 hr later by high- resolution histopathology along a defined airway path extending from the trachea to the terminal bronchioles. At 25 mg/kg, only nonciliated cells in minor daughter airways were swollen and necrotic. At 50 mg/kg there was near complete loss of nonciliated cells in most bronchioles, minor daughter airways, and tracheas. Marked damage to ciliated cells was observed at doses of 100 and 150 mg/kg. Denudation of the basement membrane was common in the trachea. We conclude for 1-nitronaphthalene cytotoxicity in the lung that: (1) nonciliated cells of the distal bronchioles are not the only target, (2) the threshold for injury in nonciliated cells is lower than that for ciliated cells, (3) the response is airway selective, (4) the response is dose- related.",
author = "Renee Paige and Viviana Wong and Charles Plopper",
year = "1997",
month = "1",
day = "1",
doi = "10.1006/taap.1997.8297",
language = "English (US)",
volume = "147",
pages = "224--233",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats

AU - Paige, Renee

AU - Wong, Viviana

AU - Plopper, Charles

PY - 1997/1/1

Y1 - 1997/1/1

N2 - Nonciliated ('Clara') cells of terminal bronchioles are one of the principal targets of bioactivated pulmonary toxicants. However, we have recently observed cytotoxicity in proximal tracheobronchial airways with high doses of naphthalene. To test if this was true for other xenobiotics, 1- nitronaphthalene (25, 50, 100, or 150 mg/kg) was injected ip into male Sprague-Dawley rats and cytotoxicity characterized 24 hr later by high- resolution histopathology along a defined airway path extending from the trachea to the terminal bronchioles. At 25 mg/kg, only nonciliated cells in minor daughter airways were swollen and necrotic. At 50 mg/kg there was near complete loss of nonciliated cells in most bronchioles, minor daughter airways, and tracheas. Marked damage to ciliated cells was observed at doses of 100 and 150 mg/kg. Denudation of the basement membrane was common in the trachea. We conclude for 1-nitronaphthalene cytotoxicity in the lung that: (1) nonciliated cells of the distal bronchioles are not the only target, (2) the threshold for injury in nonciliated cells is lower than that for ciliated cells, (3) the response is airway selective, (4) the response is dose- related.

AB - Nonciliated ('Clara') cells of terminal bronchioles are one of the principal targets of bioactivated pulmonary toxicants. However, we have recently observed cytotoxicity in proximal tracheobronchial airways with high doses of naphthalene. To test if this was true for other xenobiotics, 1- nitronaphthalene (25, 50, 100, or 150 mg/kg) was injected ip into male Sprague-Dawley rats and cytotoxicity characterized 24 hr later by high- resolution histopathology along a defined airway path extending from the trachea to the terminal bronchioles. At 25 mg/kg, only nonciliated cells in minor daughter airways were swollen and necrotic. At 50 mg/kg there was near complete loss of nonciliated cells in most bronchioles, minor daughter airways, and tracheas. Marked damage to ciliated cells was observed at doses of 100 and 150 mg/kg. Denudation of the basement membrane was common in the trachea. We conclude for 1-nitronaphthalene cytotoxicity in the lung that: (1) nonciliated cells of the distal bronchioles are not the only target, (2) the threshold for injury in nonciliated cells is lower than that for ciliated cells, (3) the response is airway selective, (4) the response is dose- related.

UR - http://www.scopus.com/inward/record.url?scp=0031413514&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031413514&partnerID=8YFLogxK

U2 - 10.1006/taap.1997.8297

DO - 10.1006/taap.1997.8297

M3 - Article

C2 - 9439718

AN - SCOPUS:0031413514

VL - 147

SP - 224

EP - 233

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 2

ER -