Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1978 Oct;93(1):183–200.

Cytologic responses of postnatal rat lungs to O3 or NO2 exposure.

R J Stephens, M F Sloan, D G Groth, D S Negi, K D Lunan
PMCID: PMC2018339  PMID: 696804

Abstract

At the level of exposure employed (approximately 14.0 ppm NO2 or 0.85 ppm O3) epithelial cells at the juncture of the terminal airways and proximal alveoli have previously been shown to be seriously injured or destroyed in maturing (35 days of age or older) and adult lungs. Subsequent repair results in the formation of a tissue nodule at this location. In contrast, postnatal rats between birth and weaning have been shown to be highly resistant to the cytotoxic effects of both NO2 and O3. Prior to wearning, exposure to O3 resulted in little or no injury when examined with either the light or electron microscope, and only minor injury and loss of cilia from epithelial cells lining the terminal airways was noted after NO2 exposure. Subsequent to weaning at 20 days of age, however, there was a progressive increase in the cellular response in both the terminal airways and proximal alveoli after exposure to either oxidant gas. A plateau in the response is reached at approximately 35 days of age and continues until the animals are approximately 1 year old. The data are discussed in terms of current theories on endogenous antioxidant mechanisms.

Full text

PDF
183

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Avery M. E. The J. Burns Amberson Lecture--in pursuit of understanding the first breath. Am Rev Respir Dis. 1969 Sep;100(3):295–304. doi: 10.1164/arrd.1969.100.3.295. [DOI] [PubMed] [Google Scholar]
  2. Bils R. F. Ultrastructural alterations of alveolar tissue of mice. 3. Ozone. Arch Environ Health. 1970 Apr;20(4):468–480. doi: 10.1080/00039896.1970.10665624. [DOI] [PubMed] [Google Scholar]
  3. Burri P. H. The postnatal growth of the rat lung. 3. Morphology. Anat Rec. 1974 Sep;180(1):77–98. doi: 10.1002/ar.1091800109. [DOI] [PubMed] [Google Scholar]
  4. Chow C. K., Tappel A. L. Activities of pentose shunt and glycolytic enzymes in lungs of ozone-exposed rats. Arch Environ Health. 1973 Apr;26(4):205–208. doi: 10.1080/00039896.1973.10666257. [DOI] [PubMed] [Google Scholar]
  5. Clark J. M., Lambertsen C. J. Pulmonary oxygen toxicity: a review. Pharmacol Rev. 1971 Jun;23(2):37–133. [PubMed] [Google Scholar]
  6. DONE A. K. DEVELOPMENTAL PHARMACOLOGY. Clin Pharmacol Ther. 1964 Jul-Aug;5:432–479. doi: 10.1002/cpt196454432. [DOI] [PubMed] [Google Scholar]
  7. Done A. K. Perinatal pharmacology. Annu Rev Pharmacol. 1966;6:189–208. doi: 10.1146/annurev.pa.06.040166.001201. [DOI] [PubMed] [Google Scholar]
  8. Evans M. J., Cabral L. J., Stephens R. J., Freeman G. Renewal of alveolar epithelium in the rat following exposure to NO2. Am J Pathol. 1973 Feb;70(2):175–198. [PMC free article] [PubMed] [Google Scholar]
  9. Evans M. J., Johnson L. V., Stephens R. J., Freeman G. Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab Invest. 1976 Sep;35(3):246–257. [PubMed] [Google Scholar]
  10. Freeman G., Crane S. C., Stephens R. J., Furiosi N. J. Environmental factors in emphysema and a model system with NO.2. Yale J Biol Med. 1968 Apr-Jun;40(5-6):566–575. [PMC free article] [PubMed] [Google Scholar]
  11. Freeman G., Crane S. C., Stephens R. J., Furiosi N. J. Pathogenesis of the nitrogen dioxide-induced lesion in the rat lung: a review and presentation of new observations. Am Rev Respir Dis. 1968 Sep;98(3):429–443. doi: 10.1164/arrd.1968.98.3.429. [DOI] [PubMed] [Google Scholar]
  12. Freeman G., Juhos L. T., Furiosi N. J., Mussenden R., Stephens R. J., Evans M. J. Pathology of pulmonary disease from exposure to interdependent ambient gases (nitrogen dioxide and ozone). Arch Environ Health. 1974 Oct;29(4):203–210. doi: 10.1080/00039896.1974.10666569. [DOI] [PubMed] [Google Scholar]
  13. Gluck L., Sribney M., Kulovich M. V. The biochemical development of surface activity in mammalian lung. II. The biosynthesis of phospholipids in the lung of the developing rabbit fetus and newborn. Pediatr Res. 1967 Jul;1(4):247–265. doi: 10.1203/00006450-196707000-00002. [DOI] [PubMed] [Google Scholar]
  14. Gregory A. R., Hine C. H. Neonatal resistance to lung edema. Proc Soc Exp Biol Med. 1968 Jul;128(3):693–695. doi: 10.3181/00379727-128-33102. [DOI] [PubMed] [Google Scholar]
  15. Haydon G. B., Freeman G., Furiosi N. J. Covert pathogenesis of NO2 induced emphysema in the rat. Arch Environ Health. 1965 Dec;11(6):776–783. doi: 10.1080/00039896.1965.10664300. [DOI] [PubMed] [Google Scholar]
  16. Leon H. A., Brooksby G. A., Chackerian M. J., Staley R. W. Nutritional and hormonal aspects of the oxygen toxicity syndrome. Aerosp Med. 1971 May;42(5):512–517. [PubMed] [Google Scholar]
  17. Ludwin S. K., Northway W. H., Jr, Bensch K. G. Oxygen toxicity in the newborn. Necrotizing bronchiolitis in mice exposed to 100 per cent oxygen. Lab Invest. 1974 Nov;31(5):425–435. [PubMed] [Google Scholar]
  18. Parkinson D. R., Stephens R. J. Morphological surface changes in the terminal bronchiolar region of NO2-exposed rat lung. Environ Res. 1973 Mar;6(1):37–51. doi: 10.1016/0013-9351(73)90015-7. [DOI] [PubMed] [Google Scholar]
  19. STOKINGER H. E. OZONE TOXICOLOGY. A REVIEW OF RESEARCH AND INDUSTRIAL EXPERIENCE: 1954-1964. Arch Environ Health. 1965 May;10:719–731. doi: 10.1080/00039896.1965.10664082. [DOI] [PubMed] [Google Scholar]
  20. STOKINGER H. E. Ozone toxicity; a review of the literature through 1953. AMA Arch Ind Hyg Occup Med. 1954 May;9(5):366–383. [PubMed] [Google Scholar]
  21. Sperling D. R. Hyperbaric oxygen toxicity in newborn and developing mice. J Appl Physiol. 1970 Oct;29(4):472–474. doi: 10.1152/jappl.1970.29.4.472. [DOI] [PubMed] [Google Scholar]
  22. Stephens R. J., Evans M. J. Selection and orientation of lung tissue for scanning and transmission electron microscopy. Environ Res. 1973 Mar;6(1):52–59. doi: 10.1016/0013-9351(73)90016-9. [DOI] [PubMed] [Google Scholar]
  23. Stephens R. J., Evans M. J., Sloan M. F., Freeman G. A comprehensive ultrastructural study of pulmonary injury and repair in the rat resulting from exposures to less than one PPM ozone. Chest. 1974 Apr;65(Suppl):11S–13S. doi: 10.1378/chest.65.4_supplement.11s. [DOI] [PubMed] [Google Scholar]
  24. Stephens R. J., Freeman G., Crane S. C., Furiosi N. J. Ultrastructural changes in the terminal bronchiole of the rat during continuous, low-level exposure to nitrogen dioxide. Exp Mol Pathol. 1971 Feb;14(1):1–19. doi: 10.1016/0014-4800(71)90048-7. [DOI] [PubMed] [Google Scholar]
  25. Stephens R. J., Freeman G., Evans M. J. Early response of lungs to low levels of nitrogen dioxide. Light and electron microscopy. Arch Environ Health. 1972 Mar;24(3):160–179. doi: 10.1080/00039896.1972.10666066. [DOI] [PubMed] [Google Scholar]
  26. Stephens R. J., Freeman G., Evans M. J. Ultrastructural changes in connective tissue in lungs of rats exposed to NO 2 . Arch Intern Med. 1971 May;127(5):873–883. [PubMed] [Google Scholar]
  27. Stephens R. J., Sloan M. F., Evans M. J., Freeman G. Alveolar type 1 cell response to exposure to 0.5 PPM O3 for short periods. Exp Mol Pathol. 1974 Feb;20(1):11–23. doi: 10.1016/0014-4800(74)90039-2. [DOI] [PubMed] [Google Scholar]
  28. Stephens R. J., Sloan M. F., Evans M. J., Freeman G. Early response of lung to low levels of ozone. Am J Pathol. 1974 Jan;74(1):31–58. [PMC free article] [PubMed] [Google Scholar]
  29. THORP C. E. The toxicity of ozone; a report and bibliography. Ind Med Surg. 1950 Feb;19(2):49–57. [PubMed] [Google Scholar]
  30. Thurlbeck W. M. Postnatal growth and development of the lung. Am Rev Respir Dis. 1975 Jun;111(6):803–844. doi: 10.1164/arrd.1975.111.6.803. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES