Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1995 Apr;146(4):1008–1016.

Cellular kinetics in the lungs of aging Fischer 344 rats after acute exposure to ozone.

R Vincent 1, I Y Adamson 1
PMCID: PMC1869255  PMID: 7717445

Abstract

Lung repair in aging Fischer 344 male rats was investigated after an acute inhalation exposure to ozone. Adult (9-month-old) and senescent (24-month-old) rats were exposed to 0.8 ppm ozone for a single period of 6 hours, and thereafter studied over 5 days of recovery in clean air. The animals were given intraperitoneal injections of colchicine and [3H]thymidine, 4 hours and 1.5 hours before termination, respectively. The lungs were inflated with glutaraldehyde, and tissue samples were embedded in epoxy resin for electron microscopy, or in glycol methacrylate for light-microscopic autoradiography. Exposure to ozone produced epithelial injury in alveolar ducts and terminal bronchioles, later reflected by the transient increase in mitotic activity of nonciliated bronchiolar cells and alveolar type 2 cells. The increase in metaphase-arrested cells and [3H]thymidine-labeled cells in bronchioles followed similar time courses, ie, maximal at days 1.5 to 2, and subsiding by day 3. In the alveoli, type 1 cell necrosis was observed early after exposure (6 hours recovery), without notable structural changes in the interstitial and endothelial compartments. The increased mitotic activity in the alveolar septa was mostly due to proliferation of epithelial type 2 cells, which was maximal at day 1.5, and of interstitial cells, maximal at day 2.5. The magnitude of the mitotic responses of nonciliated bronchiolar cells, alveolar type 2 cells and interstitial cells was highest (+50%) in the lungs of senescent rats. Although the cellular events during repair are essentially similar in both age groups, the results indicate that senescent rats have a significantly higher level of initial injury from inhalation of ozone than adult animals.

Full text

PDF
1008

Images in this article

Selected References

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

  1. Adamson I. Y., Bowden D. H. The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest. 1974 Jan;30(1):35–42. [PubMed] [Google Scholar]
  2. Adamson I. Y., Hedgecock C., Bowden D. H. Epithelial cell-fibroblast interactions in lung injury and repair. Am J Pathol. 1990 Aug;137(2):385–392. [PMC free article] [PubMed] [Google Scholar]
  3. Barry B. E., Mercer R. R., Miller F. J., Crapo J. D. Effects of inhalation of 0.25 ppm ozone on the terminal bronchioles of juvenile and adult rats. Exp Lung Res. 1988;14(2):225–245. doi: 10.3109/01902148809115126. [DOI] [PubMed] [Google Scholar]
  4. Barry B. E., Miller F. J., Crapo J. D. Effects of inhalation of 0.12 and 0.25 parts per million ozone on the proximal alveolar region of juvenile and adult rats. Lab Invest. 1985 Dec;53(6):692–704. [PubMed] [Google Scholar]
  5. Boorman G. A., Schwartz L. W., Dungworth D. L. Pulmonary effects of prolonged ozone insult in rats. Morphometric evaluation of the central acinus. Lab Invest. 1980 Aug;43(2):108–115. [PubMed] [Google Scholar]
  6. Cabral-Anderson L. J., Evans M. J., Freeman G. Effects of NO2 on the lungs of rats. I. Morphology. Exp Mol Pathol. 1977 Dec;27(3):353–365. doi: 10.1016/0014-4800(77)90006-5. [DOI] [PubMed] [Google Scholar]
  7. Chang L. Y., Huang Y., Stockstill B. L., Graham J. A., Grose E. C., Menache M. G., Miller F. J., Costa D. L., Crapo J. D. Epithelial injury and interstitial fibrosis in the proximal alveolar regions of rats chronically exposed to a simulated pattern of urban ambient ozone. Toxicol Appl Pharmacol. 1992 Aug;115(2):241–252. doi: 10.1016/0041-008X(92)90329-Q. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Evans M. J., Cabral-Anderson L. J., Freeman G. Effects of NO2 on the lungs of aging rats. II. Cell proliferation. Exp Mol Pathol. 1977 Dec;27(3):366–376. doi: 10.1016/0014-4800(77)90007-7. [DOI] [PubMed] [Google Scholar]
  9. Evans M. J., Dekker N. P., Cabral-Anderson L. J., Freeman G. Quantitation of damage to the alveolar epithelium by means of type 2 cell proliferation. Am Rev Respir Dis. 1978 Oct;118(4):787–790. doi: 10.1164/arrd.1978.118.4.787. [DOI] [PubMed] [Google Scholar]
  10. Evans M. J., Johnson L. V., Stephens R. J., Freeman G. Cell renewal in the lungs of rats exposed to low levels of ozone. Exp Mol Pathol. 1976 Feb;24(1):70–83. doi: 10.1016/0014-4800(76)90058-7. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Evans M. J., Mayr W., Bils R. F., Loosli C. G. Effects of ozone on cell renewal in pulmonary alveoli of aging mice. Arch Environ Health. 1971 Apr;22(4):450–453. doi: 10.1080/00039896.1971.10665877. [DOI] [PubMed] [Google Scholar]
  13. Evans M. J., Stephens R. J., Cabral L. J., Freeman G. Cell renewal in the lungs of rats exposed to low levels of NO2. Arch Environ Health. 1972 Mar;24(3):180–188. doi: 10.1080/00039896.1972.10666067. [DOI] [PubMed] [Google Scholar]
  14. Fischer V. W., LaRose L. S., Wang G. M. Mitigating effects of ICRF-159 (razoxane) on a daunomycin-induced cardiomyopathy in mice. Drug Chem Toxicol. 1982;5(2):155–164. doi: 10.3109/01480548209017776. [DOI] [PubMed] [Google Scholar]
  15. Hatch G. E., Slade R., Harris L. P., McDonnell W. F., Devlin R. B., Koren H. S., Costa D. L., McKee J. Ozone dose and effect in humans and rats. A comparison using oxygen-18 labeling and bronchoalveolar lavage. Am J Respir Crit Care Med. 1994 Sep;150(3):676–683. doi: 10.1164/ajrccm.150.3.8087337. [DOI] [PubMed] [Google Scholar]
  16. Hazzard D. G., Soban J. Addendum to: studies of aging using defined rodents: a bibliography. Exp Aging Res. 1991 Spring;17(1):53–61. doi: 10.1080/03610739108253885. [DOI] [PubMed] [Google Scholar]
  17. Kozumbo W. J., Agarwal S. Induction of DNA damage in cultured human lung cells by tobacco smoke arylamines exposed to ambient levels of ozone. Am J Respir Cell Mol Biol. 1990 Dec;3(6):611–618. doi: 10.1165/ajrcmb/3.6.611. [DOI] [PubMed] [Google Scholar]
  18. Lippmann M. Health effects of tropospheric ozone: review of recent research findings and their implications to ambient air quality standards. J Expo Anal Environ Epidemiol. 1993 Jan-Mar;3(1):103–129. [PubMed] [Google Scholar]
  19. Montgomery M. R., Raska-Emery P., Balis J. U. Age-related difference in pulmonary response to ozone. Biochim Biophys Acta. 1987 Feb 11;890(2):271–274. doi: 10.1016/0005-2728(87)90028-4. [DOI] [PubMed] [Google Scholar]
  20. Pinkerton K. E., Barry B. E., O'Neil J. J., Raub J. A., Pratt P. C., Crapo J. D. Morphologic changes in the lung during the lifespan of Fischer 344 rats. Am J Anat. 1982 Jun;164(2):155–174. doi: 10.1002/aja.1001640206. [DOI] [PubMed] [Google Scholar]
  21. Pinkerton K. E., Mercer R. R., Plopper C. G., Crapo J. D. Distribution of injury and microdosimetry of ozone in the ventilatory unit of the rat. J Appl Physiol (1985) 1992 Sep;73(3):817–824. doi: 10.1152/jappl.1992.73.3.817. [DOI] [PubMed] [Google Scholar]
  22. Plopper C. G., Chu F. P., Haselton C. J., Peake J., Wu J., Pinkerton K. E. Dose-dependent tolerance to ozone. I. Tracheobronchial epithelial reorganization in rats after 20 months' exposure. Am J Pathol. 1994 Feb;144(2):404–420. [PMC free article] [PubMed] [Google Scholar]
  23. Rajini P., Gelzleichter T. R., Last J. A., Witschi H. Alveolar and airway cell kinetics in the lungs of rats exposed to nitrogen dioxide, ozone, and a combination of the two gases. Toxicol Appl Pharmacol. 1993 Aug;121(2):186–192. doi: 10.1006/taap.1993.1144. [DOI] [PubMed] [Google Scholar]
  24. Rasmussen R. E. Inhibition of DNA replication by ozone in Chinese hamster V79 cells. J Toxicol Environ Health. 1986;17(1):119–128. doi: 10.1080/15287398609530807. [DOI] [PubMed] [Google Scholar]
  25. Witschi H., Cöté M. G. Inhibition of butylated hydroxytoluene-induced mouse lung cell division by oxygen: time-effect and dose-effect relationships. Chem Biol Interact. 1977 Dec;19(3):279–289. doi: 10.1016/0009-2797(77)90051-5. [DOI] [PubMed] [Google Scholar]

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

RESOURCES