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. 1983 Apr;111(1):56–61.

An ultrastructural study of bronchiolar lesions in rats induced by 4-ipomeanol, a product from mold-damaged sweet potatoes.

A R Doster, R L Farrell, B J Wilson
PMCID: PMC1916208  PMID: 6837724

Abstract

Repeated intraperitoneal injections of 4-ipomeanol in rats resulted in extensive degeneration and necrosis of nonciliated (Clara) bronchiolar epithelial cells. Subsequently there was necrosis and detachment of ciliated cells from the bronchiolar basal lamina. The remaining nonciliated cells divided and differentiated into ciliated epithelial cells and mature Clara cells. The ability of Clara cells to metabolize certain xenobiotics suggests that they may play an important role in the pathogenesis of pulmonary disease and neoplasia.

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Selected References

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

  1. Allen J. G., Seawright A. A., Hrdlicka J. The toxicity of myoporum tetrandrum (Boobialla) and myoporaceous furanoid essential oils for ruminants. Aust Vet J. 1978 Jun;54(6):287–292. doi: 10.1111/j.1751-0813.1978.tb02461.x. [DOI] [PubMed] [Google Scholar]
  2. Azzopardi A., Thurlbeck W. M. The histochemistry of the nonciliated bronchiolar epithelial cell. Am Rev Respir Dis. 1969 Apr;99(4):516–525. doi: 10.1164/arrd.1969.99.4P1.516. [DOI] [PubMed] [Google Scholar]
  3. Boyd M. R., Burka L. T., Harris T. M., Wilson B. J. Lung-toxic furanoterpenoids produced by sweet potatoes (Ipomoea batatas) following microbial infection. Biochim Biophys Acta. 1974 Feb 25;337(2):184–195. doi: 10.1016/0005-2760(74)90200-8. [DOI] [PubMed] [Google Scholar]
  4. Boyd M. R. Evidence for the Clara cell as a site of cytochrome P450-dependent mixed-function oxidase activity in lung. Nature. 1977 Oct 20;269(5630):713–715. doi: 10.1038/269713a0. [DOI] [PubMed] [Google Scholar]
  5. Boyd M. R., Statham C. N., Franklin R. B., Mitchell J. R. Pulmonary bronchiolar alkylation and necrosis by 3-methylfuran, a naturally occurring potential atmospheric contaminant. Nature. 1978 Mar 16;272(5650):270–271. doi: 10.1038/272270a0. [DOI] [PubMed] [Google Scholar]
  6. Boyd M. R., Statham C. N., Longo N. S. The pulmonary clara cell as a target for toxic chemicals requiring metabolic activation; studies with carbon tetrachloride. J Pharmacol Exp Ther. 1980 Jan;212(1):109–114. [PubMed] [Google Scholar]
  7. Breeze R. G., Wheeldon E. B. The cells of the pulmonary airways. Am Rev Respir Dis. 1977 Oct;116(4):705–777. doi: 10.1164/arrd.1977.116.4.705. [DOI] [PubMed] [Google Scholar]
  8. Campbell T. C., Hayes J. R. The role of aflatoxin metabolism in its toxic lesion. Toxicol Appl Pharmacol. 1976 Feb;35(2):199–222. doi: 10.1016/0041-008x(76)90282-9. [DOI] [PubMed] [Google Scholar]
  9. Cutz E., Conen P. E. Ultrastructure and cytochemistry of Clara cells. Am J Pathol. 1971 Jan;62(1):127–141. [PMC free article] [PubMed] [Google Scholar]
  10. Doster A. R., Mitchell F. E., Farrell R. L., Wilson B. J. Effects of 4-ipomeanol, a product from mold-damaged sweet potatoes, on the bovine lung. Vet Pathol. 1978 May;15(3):367–375. doi: 10.1177/030098587801500312. [DOI] [PubMed] [Google Scholar]
  11. Evans M. J., Cabral-Anderson L. J., Freeman G. Role of the Clara cell in renewal of the bronchiolar epithelium. Lab Invest. 1978 Jun;38(6):648–653. [PubMed] [Google Scholar]
  12. 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]
  13. Gram T. E. Comparative aspects of mixed function oxidation by lung and liver of rabbits. Drug Metab Rev. 1973;2(1):1–32. doi: 10.3109/03602537409030003. [DOI] [PubMed] [Google Scholar]
  14. Guengerich F. P. Studies on the activation of a model furan compound--toxicity and covalent binding of 2-(N-ethylcarbamoylhydroxymethyl)furan. Biochem Pharmacol. 1977 Oct 15;26(20):1909–1915. doi: 10.1016/0006-2952(77)90165-4. [DOI] [PubMed] [Google Scholar]
  15. Hook G. E., Bend J. R., Hoel D., Fouts J. R., Gram T. E. Preparation of lung microsomes and a comparison of the distribution of enzymes between subcellular fractions of rabbit lung and liver. J Pharmacol Exp Ther. 1972 Sep;182(3):474–490. [PubMed] [Google Scholar]
  16. Jeffery P. K., Reid L. New observations of rat airway epithelium: a quantitative and electron microscopic study. J Anat. 1975 Nov;120(Pt 2):295–320. [PMC free article] [PubMed] [Google Scholar]
  17. Kuhn C., 3rd, Callaway L. A., Askin F. B. The formation of granules in the bronchiolar Clara cells of the rat. 1. Electron microscopy,. J Ultrastruct Res. 1974 Dec;49(3):387–400. doi: 10.1016/s0022-5320(74)90052-5. [DOI] [PubMed] [Google Scholar]
  18. Lum H., Schwartz L. W., Dungworth D. L., Tyler W. S. A comparative study of cell renewal after exposure to ozone or oxygen. Response of terminal bronchiolar epithelium in the rat. Am Rev Respir Dis. 1978 Aug;118(2):335–345. doi: 10.1164/arrd.1978.118.2.335. [DOI] [PubMed] [Google Scholar]
  19. Mahvi D., Bank H., Harley R. Morphology of a naphthalene-induced bronchiolar lesion. Am J Pathol. 1977 Mar;86(3):558–572. [PMC free article] [PubMed] [Google Scholar]
  20. McMurtry R. J., Mitchell J. R. Renal and hepatic necrosis after metabolic activation of 2-substituted furans and thiophenes, including furosemide and cephaloridine. Toxicol Appl Pharmacol. 1977 Nov;42(2):285–300. doi: 10.1016/0041-008x(77)90005-9. [DOI] [PubMed] [Google Scholar]
  21. Miller E. C. Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. Cancer Res. 1978 Jun;38(6):1479–1496. [PubMed] [Google Scholar]
  22. Miller J. A., Miller E. C. Carcinogens occurring naturally in foods. Fed Proc. 1976 May 1;35(6):1316–1321. [PubMed] [Google Scholar]
  23. Mitchell J. R., Nelson W. L., Potter W. Z., Sasame H. A., Jollow D. J. Metabolic activation of furosemide to a chemically reactive, hepatotoxic metabolite. J Pharmacol Exp Ther. 1976 Oct;199(1):41–52. [PubMed] [Google Scholar]
  24. Oppelt W. W., Zange M., Ross W. E., Remmer H. Comparison of microsomal drug hydroxylation in lung and liver of various species. Res Commun Chem Pathol Pharmacol. 1970 Jan;1(1):43–56. [PubMed] [Google Scholar]
  25. Reid W. D., Ilett K. F., Glick J. M., Krishna G. Metabolism and binding of aromatic hydrocarbons in the lung. Relationship to experimental bronchiolar necrosis. Am Rev Respir Dis. 1973 Apr;107(4):539–551. doi: 10.1164/arrd.1973.107.4.539. [DOI] [PubMed] [Google Scholar]
  26. Reznik-Schüller H. Ultrastructural alterations of nonciliated cells after nitrosamine treatment and their significance for pulmonary carcinogenesis. Am J Pathol. 1976 Dec;85(3):549–554. [PMC free article] [PubMed] [Google Scholar]
  27. Reznik-Schüller H. Ultrastructure of nitrosoheptamethyleneimine-induced lung tumors in European hamsters. Am J Pathol. 1978 Oct;93(1):45–52. [PMC free article] [PubMed] [Google Scholar]
  28. Said S. I. The lung as a metabolic organ. N Engl J Med. 1968 Dec 12;279(24):1330–1334. doi: 10.1056/NEJM196812122792409. [DOI] [PubMed] [Google Scholar]
  29. Seawright A. A., Mattocks A. R. The toxicity of two synthetic 3-substituted furan carbamates. Experientia. 1973 Oct 15;29(10):1197–1200. doi: 10.1007/BF01935068. [DOI] [PubMed] [Google Scholar]
  30. Smith P., Heath D., Moosavi H. The Clara cell. Thorax. 1974 Mar;29(2):147–163. doi: 10.1136/thx.29.2.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spurr A. R. A low-viscosity epoxy resin embedding medium for electron microscopy. J Ultrastruct Res. 1969 Jan;26(1):31–43. doi: 10.1016/s0022-5320(69)90033-1. [DOI] [PubMed] [Google Scholar]
  32. Wang N. S., Huang S. N., Sheldon H., Thurlbeck W. M. Ultrastructural changes of Clara and type II alveolar cells in adrenalin-induced pulmonary edema in mice. Am J Pathol. 1971 Feb;62(2):237–252. [PMC free article] [PubMed] [Google Scholar]
  33. Yoneda K. Pilocarpine stimulation of the bronchiolar Clara cell secretion. Lab Invest. 1977 Nov;37(5):447–452. [PubMed] [Google Scholar]
  34. Yoneda K. Ultrastructural localization of phospholipases in the Clara cell of the rat bronchiole. Am J Pathol. 1978 Dec;93(3):745–752. [PMC free article] [PubMed] [Google Scholar]

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