Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1985 Oct;121(1):128–137.

Pulmonary lesions induced by 3-methylindole in mice.

S K Durham, W L Castleman
PMCID: PMC1888027  PMID: 4050971

Abstract

The morphogenesis of pulmonary lesions and associated edema induced by the pulmonary toxicant 3-methylindole (3-MI) was studied by combined light and transmission electron microscopy. Weanling male CD-1 mice received 3-MI dissolved in corn oil by intraperitoneal injection and were studied at intervals from 2 to 360 hours after treatment. Interstitial edema was observed as early as 2 hours and was associated with focal cytoplasmic swelling and membrane alterations in both capillary endothelial cells and Type I alveolar epithelial cells and with sequestration of neutrophils. Cell swelling, cytoplasmic fragmentation, and necrosis of Type I epithelial cells was most severe at 24-48 hours after treatment. Multifocal hypertrophy and hyperplasia of Type II alveolar epithelial cells was observed at 24-96 hours after treatment. Platelet aggregation and aggregates of fibrin were frequently observed in capillaries and small arteries and veins as early as 4 hours and as late as 48 hours after treatment. In airways, the nonciliated bronchiolar epithelial (Clara) cell was the predominant cell affected. Initial lesions in nonciliated cells consisted of loss of microvilli and secretory granules followed by marked swelling of the endoplasmic reticulum and mitochondria. Necrosis of cells lining airways was most pronounced at 24-48 hours after treatment. By 144 hours after administration, pulmonary repair was complete. It is concluded that the mouse is a useful model of 3-MI-induced pulmonary injury and that damage to both Type I alveolar epithelial cells and capillary endothelial cells is important in the pathogenesis of 3-MI-induced pulmonary edema.

Full text

PDF
128

Images in this article

130Figure 1
on p.130
130Figure 2
on p.130
130Figure 3
on p.130
130Figure 4
on p.130
130Figure 5
on p.130
130Figure 6
on p.130
131Figure 7
on p.131
131Figure 8
on p.131
132Figure 9
on p.132
132Figure 10
on p.132
133Figure 11
on p.133
134Figure 12
on p.134
134Figure 13
on p.134
134Figure 14
on p.134
135Figure 15
on p.135
136Figure 16
on p.136
136Figure 17
on p.136
136Figure 18
on p.136
136Figure 19
on p.136

Selected References

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

  1. Atwal O. S., Persofsky M. S. Ultrastructural changes in intraacinar pulmonary veins. Relationship to 3-methylindole-induced acute pulmonary edema and pulmonary arterial changes in cattle. Am J Pathol. 1984 Mar;114(3):472–486. [PMC free article] [PubMed] [Google Scholar]
  2. Atwal O. S., Persofsky M. S. Ultrastructural pathology of intrapulmonary arteries in 3-methylindole-induced pneumotoxicity in cattle: II. Glycogen accumulation in the smooth muscle cells and intimal changes. J Pathol. 1984 Feb;142(2):141–149. doi: 10.1002/path.1711420205. [DOI] [PubMed] [Google Scholar]
  3. Atwal O. S. Ultrastructural pathology of 3-methylindole-induced pneumotoxicity in cattle. I. Glycogen accumulation in the alveolar type II cells and tubular myelin accumulation in the alveoli. J Submicrosc Cytol. 1983 Apr;15(2):433–445. [PubMed] [Google Scholar]
  4. Boyd M. R. Biochemical mechanisms in chemical-induced lung injury: roles of metabolic activation. Crit Rev Toxicol. 1980 Aug;7(2):103–176. doi: 10.3109/10408448009037487. [DOI] [PubMed] [Google Scholar]
  5. Boyd M. R., Stiko A., Statham C. N., Jones R. B. Protective role of endogenous pulmonary glutathione and other sulfhydryl compounds against lung damage by alkylating agents. Investigations with 4-ipomeanol in the rat. Biochem Pharmacol. 1982 Apr 15;31(8):1579–1583. doi: 10.1016/0006-2952(82)90383-5. [DOI] [PubMed] [Google Scholar]
  6. Bradley B. J., Carlson J. R., Dickinson E. O. 3-methylindole-induced pulmonary edema and emphysema in sheep. Am J Vet Res. 1978 Aug;39(8):1355–1358. [PubMed] [Google Scholar]
  7. Bradley B. J., Carlson J. R. Ultrastructural pulmonary changes induced by intravenously administered 3-methylindole in goats. Am J Pathol. 1980 Jun;99(3):551–560. [PMC free article] [PubMed] [Google Scholar]
  8. Bray T. M., Carlson J. R. Role of mixed-function oxidase in 3-methylindole-induced acute pulmonary edema in goats. Am J Vet Res. 1979 Sep;40(9):1268–1272. [PubMed] [Google Scholar]
  9. Breeze R. G., Carlson J. R. Chemical-induced lung injury in domestic animals. Adv Vet Sci Comp Med. 1982;26:201–231. [PubMed] [Google Scholar]
  10. Breeze R. G., Pirie H. M., Selman I. E., Wiseman A. Fog fever in cattle: cytology of the hyperplastic alveolar epithelium. J Comp Pathol. 1975 Jan;85(1):147–156. doi: 10.1016/0021-9975(75)90093-6. [DOI] [PubMed] [Google Scholar]
  11. Burley F. E., Bray T. M. Effect of dietary vitamin A on the mixed function oxidases and the pneumotoxicity of 3-methylindole in goats. Can J Physiol Pharmacol. 1983 Aug;61(8):816–821. doi: 10.1139/y83-125. [DOI] [PubMed] [Google Scholar]
  12. Carlson J. R., Dickinson E. O., Yokoyama M. T., Bradley B. Pulmonary edema and emphysema in cattle after intraruminal and intravenous administration of 3-methylindole. Am J Vet Res. 1975 Sep;36(9):1341–1347. [PubMed] [Google Scholar]
  13. Carlson J. R., Yokoyama M. T., Dickinson E. O. Induction of pulmonary edema and emphysema in cattle and goats with 3-methylindole. Science. 1972 Apr 21;176(4032):298–299. doi: 10.1126/science.176.4032.298. [DOI] [PubMed] [Google Scholar]
  14. Cockerell G. L., Gilmartin J. E., Albern W. F., Losikoff A. M., Sansone E. B. Design and testing of a biocontainment system for chemical carcinogens. J Toxicol Environ Health. 1981 Jan;7(1):1–7. doi: 10.1080/15287398109529953. [DOI] [PubMed] [Google Scholar]
  15. Dickinson E. O., Yokoyama M. T., Carlson J. R., Bradley B. J. Induction of pulmonary edema and emphysema in goats by intraruminal administration of 3-methylindole. Am J Vet Res. 1976 Jun;37(6):667–672. [PubMed] [Google Scholar]
  16. Durham S. K., Boyd M. R., Castleman W. L. Pulmonary endothelial and bronchiolar epithelial lesions induced by 4-ipomeanol in mice. Am J Pathol. 1985 Jan;118(1):66–75. [PMC free article] [PubMed] [Google Scholar]
  17. Evans M. J. Oxidant gases. Environ Health Perspect. 1984 Apr;55:85–95. doi: 10.1289/ehp.845585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hanafy M. S., Bogan J. A. Pharmacological modulation of the pneumotoxicity of 3-methylindole. Biochem Pharmacol. 1982 May 1;31(9):1765–1771. doi: 10.1016/0006-2952(82)90682-7. [DOI] [PubMed] [Google Scholar]
  19. Herget J., Palecek F. Experimental chronic pulmonary hypertension. Int Rev Exp Pathol. 1978;18:347–406. [PubMed] [Google Scholar]
  20. Hislop A., Reid L. Normal structure and dimensions of the pulmonary arteries in the rat. J Anat. 1978 Jan;125(Pt 1):71–83. [PMC free article] [PubMed] [Google Scholar]
  21. Huang T. W., Carlson J. R., Bray T. M., Bradley B. J. 3-methylindole-induced pulmonary injury in goats. Am J Pathol. 1977 Jun;87(3):647–666. [PMC free article] [PubMed] [Google Scholar]
  22. Kubow S., Janzen E. G., Bray T. M. Spin-trapping of free radicals formed during in vitro and in vivo metabolism of 3-methylindole. J Biol Chem. 1984 Apr 10;259(7):4447–4451. [PubMed] [Google Scholar]
  23. Leung C. T., Carlson J. R., Breeze R. G. Effects of mixed-function oxidase inducers and inhibitors on cytochrome P-450 content, gel electrophoresis profiles, and 3-methylindole-induced lung toxicity in goats. Can J Physiol Pharmacol. 1983 Apr;61(4):395–402. doi: 10.1139/y83-060. [DOI] [PubMed] [Google Scholar]
  24. Malik A. B., Johnson A., Tahamont M. V. Mechanisms of lung vascular injury after intravascular coagulation. Ann N Y Acad Sci. 1982;384:213–234. doi: 10.1111/j.1749-6632.1982.tb21374.x. [DOI] [PubMed] [Google Scholar]
  25. Merrill J. C., Bray T. M. The effect of dietary and sulfur compounds in alleviating 3-methylindole-induced pulmonary toxicity in goats. J Nutr. 1983 Sep;113(9):1725–1731. doi: 10.1093/jn/113.9.1725. [DOI] [PubMed] [Google Scholar]
  26. Meyrick B., Reid L. Ultrastructural features of the distended pulmonary arteries of the normal rat. Anat Rec. 1979 Jan;193(1):71–97. doi: 10.1002/ar.1091930106. [DOI] [PubMed] [Google Scholar]
  27. Pirie H. M., Breeze R. G., Selman I. E., Wiseman A. Indole-acetic acid, 3-methyl indole and type 2 pneumonocyte hyperplasia in a proliferative alveolitis of cattle. Vet Rec. 1976 Mar 27;98(13):259–260. doi: 10.1136/vr.98.13.259. [DOI] [PubMed] [Google Scholar]
  28. Potchoiba M. J., Carlson J. R., Breeze R. G. Metabolism and pneumotoxicity of 3-methyloxindole, indole-3-carbinol, and 3-methylindole in goats. Am J Vet Res. 1982 Aug;43(8):1418–1423. [PubMed] [Google Scholar]
  29. Robin E. D., Cross C. E., Zelis R. Pulmonary edema. 2. N Engl J Med. 1973 Feb 8;288(6):292–304. doi: 10.1056/NEJM197302082880606. [DOI] [PubMed] [Google Scholar]
  30. Selman I. E., Wiseman A., Pirie H. M., Breeze R. G. Fog fever in cattle: clinical and epidemiological features. Vet Rec. 1974 Aug 17;95(7):139–146. doi: 10.1136/vr.95.7.139. [DOI] [PubMed] [Google Scholar]
  31. Smith P., Heath D. Ultrastructure of hypoxic hypertensive pulmonary vascular disease. J Pathol. 1977 Feb;121(2):93–100. doi: 10.1002/path.1711210205. [DOI] [PubMed] [Google Scholar]
  32. Staub N. C., Schultz E. L., Albertine K. H. Leucocytes and pulmonary microvascular injury. Ann N Y Acad Sci. 1982;384:332–343. doi: 10.1111/j.1749-6632.1982.tb21382.x. [DOI] [PubMed] [Google Scholar]
  33. Turk M. A., Flory W., Henk W. G. Dose response in 3-methylindole-induced bronchiolar epithelial necrosis in mice. Res Commun Chem Pathol Pharmacol. 1984 Dec;46(3):351–362. [PubMed] [Google Scholar]
  34. Vaage J. Intravascular platelet aggregation and pulmonary injury. Ann N Y Acad Sci. 1982;384:301–318. doi: 10.1111/j.1749-6632.1982.tb21380.x. [DOI] [PubMed] [Google Scholar]
  35. Yokoyama M. T., Carlson J. R. Dissimilation of tryptophan and related indolic compounds by ruminal microorganisms in vitro. Appl Microbiol. 1974 Mar;27(3):540–548. doi: 10.1128/am.27.3.540-548.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES