Bleomycin-induced Injury and Metaplasia of Alveolar Type 2 Cells. Relationship of Cellular Responses to Drug Presence in the Lung

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1979 Aug 1

PMID 89815

Citations 34

Authors

I Y Adamson

D H BOWDEN

Affiliations

Soon will be listed here.

Abstract

Metaplastic epithelial cells are often observed lining alveoli in bleomycin-induced pulmonary fibrosis. The hypothesis that these cellular changes are induced by the direct action of the drug on differentiating Type 2 cells is now examined in a sequential study to correlate the presence of 3H bleomycin in the lung with the pattern of injury and repair of the alveolar epithelium. A single intravenous dose or multiple small intraperitoneal doses induce focal necrosis of Type 1 epithelial cells followed by Type 2 cell regeneration. At the time of maximal deoxyribonucleic acid (DNA) synthesis in these cells, significant amounts of 3H bleomycin are demonstrable in the lung by scintillation counting; and in autoradiographs, the drug appears to concentrate in epithelial cells. Subsequently many abnormal Type 2 cells are seen. Some are binucleate, and others show nuclear disruption. The usual process of differentiation to Type 1 cells does not occur; instead, a variety of epithelial forms are found, including fetal-like tubular structures and ciliated and squamous metaplastic cells. The correlation of epithelial injury and repair with the direct demonstration of bleomycin in the lung indicates that Type 2 cells are susceptible to injury in the division and differentiation phases of the cell cycle and may then produce a variety of inappropriate alveolar lining cells.

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References

Adamson Y, BOWDEN D . Pulmonary injury and repair. Organ culture studies of murine lung after oxygen. Arch Pathol Lab Med. 1976; 100(12):640-3. View

Bedrossian C, Luna M, Mackay B, Lichtiger B . Ultrastructure of pulmonary bleomycin toxicity. Cancer. 1973; 32(1):44-51. DOI: 10.1002/1097-0142(197307)32:1<44::aid-cncr2820320106>3.0.co;2-q. View

Umezawa H . Chemistry and mechanism of action of bleomycin. Fed Proc. 1974; 33(11):2296-302. View

Adamson I, BOWDEN D . The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol. 1974; 77(2):185-97. PMC: 1910906. View

Evans M, Cabral L, Stephens R, Freeman G . Renewal of alveolar epithelium in the rat following exposure to NO2. Am J Pathol. 1973; 70(2):175-98. PMC: 1903972. View

Adamson I, BOWDEN D . The type 2 cell as progenitor of alveolar epithelial regeneration. A cytodynamic study in mice after exposure to oxygen. Lab Invest. 1974; 30(1):35-42. View

Umezawa H, Ishizuki M, Hori S, Chimura H, Takeuchi T . The distribution of 3H-bleomycin in mouse tissue. J Antibiot (Tokyo). 1968; 21(11):638-42. DOI: 10.7164/antibiotics.21.638. View

Gould V, Tosco R, Wheelis R, Gould N, KAPANCI Y . Oxygen pneumonitis in man. Ultrastructural observations on the development of alveolar lesions. Lab Invest. 1972; 26(5):499-508. View

Umezawa H, Ishizuka M, Maeda K, Takeuchi T . Studies on bleomycin. Cancer. 1967; 20(5):891-5. DOI: 10.1002/1097-0142(1967)20:5<891::aid-cncr2820200550>3.0.co;2-v. View

10.

Adamson I, BOWDEN D, WYATT J . Oxygen poisoning in mice. Ultrastructural and surfactant studies during exposure and recovery. Arch Pathol. 1970; 90(5):463-72. View

11.

Iversen P, Clausen O, Iversen U, Rohrbach R . Some effects of bleomycin on the proliferation, maturation time and protein synthesis of hairless mouse epidermis. Cell Tissue Kinet. 1976; 9(1):77-97. DOI: 10.1111/j.1365-2184.1976.tb01255.x. View

12.

YASUZUMI G, Hyo Y, Hoshiya T, Yasuzumi F . Effects of bleomycin on human tongue carcinoma cells as revealed by electron microscopy. Cancer Res. 1976; 36(10):3574-83. View

13.

Iqbal Z, Kohn K, Ewig R, Fornace Jr A . Single-strand scission and repair of DNA in mammalian cells by bleomycin. Cancer Res. 1976; 36(10):3834-8. View

14.

Caputo A . Importance of experimental data for the improvement of the therapeutical effect of bleomycin. Prog Biochem Pharmacol. 1976; 11:2-17. View

15.

Sostman H, Matthay R, Putman C . Cytotoxic drug-induced lung disease. Am J Med. 1977; 62(4):608-15. DOI: 10.1016/0002-9343(77)90424-7. View

16.

Kuo M, Auger L, Saunders G, HAIDLE C . Effect of bleomycin on the synthesis and function of RNA. Cancer Res. 1977; 37(5):1345-8. View

17.

Adamson I, BOWDEN D . Origin of ciliated alveolar epithelial cells in bleomycin-induced lung injury. Am J Pathol. 1977; 87(3):569-80. PMC: 2032137. View

18.

Lown J, Sim S . The mechanism of the bleomycin-induced cleavage of DNA. Biochem Biophys Res Commun. 1977; 77(4):1150-7. DOI: 10.1016/s0006-291x(77)80099-5. View

19.

Adamson I, BOWDEN D, Cote M, Witschi H . Lung injury induced by butylated hydroxytoluene: cytodynamic and biochemical studies in mice. Lab Invest. 1977; 36(1):26-32. View

20.

Hirai K, Witschi H, Cote M . Electron microscopy of butylated hydroxytoluene-induced lung damage in mice. Exp Mol Pathol. 1977; 27(3):295-308. DOI: 10.1016/0014-4800(77)90002-8. View