Abstract
An animal model of pulmonary radiation-induced lung injury was established in the hamster and the effects of pretreatment with recombinant human CuZn superoxide dismutase (SOD) on the development of the lesion were evaluated. Hamsters exposed to a single irradiation dose of 2000 cGy delivered to the thorax were treated with 150 mg/kg body weight of SOD or an equivalent volume of saline intraperitoneally 75 min and subcutaneously 5 min before receiving irradiation. At 4, 8, and 16 weeks following irradiation, pulmonary injury was evaluated by the grading of morphologic changes semiquantitatively, measurement of lung hydroxyproline content, and analysis of bronchoalveolar lavage fluid for total and differential cell counts and total protein concentration. Radiation-induced lung injury in saline-pretreated animals was documented at 16 weeks by histologic morphology and increased protein in bronchoalveolar lavage fluid. SOD protected against radiation-induced pulmonary injury as indicated by the absence of severe histopathologic changes and prevention of elevation in bronchoalveolar lavage protein levels. The beneficial effects of SOD in preventing radiation-induced pulmonary toxicity suggests that this recombinant enzyme may play a role in protection against radiation-induced pulmonary injury in humans.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abo M, Nishidai T, Yukawa Y, Takahashi M, Ono K, Heraoka M, Ri N (1981) Studies on the radioprotective effects of superoxide dismutase in mice. Int J Radiation Oncol Biol Phys 7:205–209
Anderson RL, Ahier RG, Coultas PG (1985) Responses of mouse lung to irradiation. 2. Levels of alveolar protein in lung lavage fluid following neutrons or X-rays. Radiother Oncol 4:167–174
Breuer R, Or R, Lijovetzky G, Naparstek D, Engelhard D, Lafair J, Weshler Z, Slavin S (1988) Interstitial pneumonitis in T cell-depleted bone marrow transplantation. Bone Marrow Transplant 3:625–630
Conner MW, Flood WH, Rogers AE, Amdur MO (1989) Changes in pulmonary lavage fluid of guina pigs exposed to ultrafine zinc oxide with adsorbed sulfuric acid. J Toxicol Environ Health 24:223–234
Fenner F (1986) In: Bhalt PN, Jacoby RD, Morse HC, New AE (eds) Viral and mycoplasmal infections of laboratory rodents. Academic Press, New York, pp 19–33
Fridovich I (1975) Superoxide dismutases. Anu Rev Biochem 44:147–159
Gross NJ (1977) Pulmonary effects of radiation therapy. Ann Intern Med 86:81–92
Gross NJ (1980) Experimental radiation pneumonitis. IV. Leakage of circulatory proteins into the alveolar surface. J Lab Clin Med 95:19–31
Hartman JR, Geller T, Yavin Z, Bartfield D, Kanner D, Aviv H, Gorecki M (1986) High level expression of enzymatically active human Cu-Zn superoxide dismutase in Escherichia coli. Proc Natl Acad Sci 83:7142–7146
Henderson RF, Benson JM, Hahn FF, Hobbs CH, Jones RK, Mauderly JL, McClellan RO, Pickrell JA (1985) New approaches for the evaluation of pulmonary toxicity: bronchoalveolar lavage fluid analysis. Fundament Appl Toxicol 5:451–458
Jackson DS, Cleary EG (1967) The determination of collagen and elastin. Methods Biochem Anal 15:25–76
Malaker K, Das RM (1988) Effect of superoxide dismutase on early radiation injury of lungs in rats. Mol Cell Biochem 84:141–145
Malaker K, Das RM (1988) The effect of superoxide dismutase on the pathogenesis of radiation-induced pulmonary damage in the rat. Pharmacol Ther 39:327–330
McCord JM, Fridovich I (1969) Superoxide dismutase. J Biol Chem 244:6049–6055
McDowell EM, Trump BF (1976) Histologic fixatives suitable for diagnostic light and electron microscopy. Arch Pathol Lab Med 100:405–414
Nieman PE, Reeves W, Ray G, et al (1977) A retrospective analysis of interstitial pneumonitis and opportunistic viral infection among recepients of allogeneic bone marrow grafts. J Infect Dis 136:754–767
Pesce MA, Strande CS (1973) A new micromethod for determination of protein in cerebrospinal fluid and urine. Clin Chem 19:1265–1267
Petkau A, Chelack WS, Pleskach SD (1976) Protection of postirradiated mice by superoxide dismutase. Int J Radiat Biol 29:297–299
Snedicor GW, Cochrane WG (1980) Statistical methods, 7th ed. Iowa State University Press, Ames, IA
Tillman BF, Loyd JE, Malcolm AW, Holm BA, Brigham KL (1989) Unilateral radiation pneumonitis in sheep: physiological changes and bronchoalveolar lavage. J Appl Physiol 66:1273–1279
Travis EL (1980) The sequence of histological changes in mouse lungs after single doses of x-rays. Int J Radiat Oncol Biol Phys 6:345–347
Vergara JA, Thet RU, Thet LA (1987) Changes in lung morphology and cell number in radiation pneumonitis and fibrosis: a quantitative ultrastructural study. Int J Radiat Oncol Biol Phys 13:723–732
Weiner RS, Bortin MM, Gale RP, Gluckman E, Kay HEM, Kolb HJ, Hartz AJ, Rimm AA (1986) Interstitial pneumonitis after bone marrow transplantation. Ann Intern Med 104:168–175
Author information
Authors and Affiliations
Additional information
Offprint requests to: R. Breuer
Rights and permissions
About this article
Cite this article
Breuer, R., Tochner, Z., Conner, M.W. et al. Superoxide dismutase inhibits radiation-induced lung injury in hamsters. Lung 170, 19–29 (1992). https://doi.org/10.1007/BF00164752
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00164752