QUANTIFICATION OF BLEOMYCIN PULMONARY TOXICITY IN MICE BY CHANGES IN LUNG HYDROXYPROLINE CONTENT AND MORPHOMETRIC HISTOPATHOLOGY

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  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (3) , 787-792
Abstract
Bleomycin treatment produced dose-dependent changes in lung collagen content and several measurable histopathological parameters. NIH/Swiss mice were treated twice weekly for 6 wk with bleomycin, 0, 1, 20 or 40 mg/kg s.c. The 2 highest doses produced mortalities of 35 and 100%, respectively, as well as loss of body weight and increase in lung wet weight. Lung hydroxyproline content, an index of collagen, increased to 40-50% above control levels at 6 and 8 wk after initiation of treatment with bleomycin 20 mg/kg. Morphometric analysis was applied to the following parameters at light microscopy: number of intraalveolar macrophages and leukocytes, total pulmonary cell count, alveolar wall thickness and percentage of consolidation of lung parenchyma. The 2 highest doses produced increases in all of these parameters as compared to controls. The most marked changes occurred in the number of intraalveolar cells, which in the group given 20 mg/kg rose to 150, 190 and 210% of controls at 4, 6 and 8 wk. The lowest dose of bleomycin, 1 mg/kg twice weekly for 6 wk, evoked no pulmonary or other toxicity by the parameters examined. This model of chronic pulmonary toxicity may be useful in analog development, testing potential antidotes and examining the effects of other factors that might modify the pulmonary toxicity of the antitumor agent bleomycin.