Biochemical and structural alterations of hamster lungs in response to intratracheal administration of bleomycin

Abstract

One unit of bleomycin was administered intratracheally to hamsters and an equivalent volume of saline to controls. Morphological changes within lungs of bleomycin-treated hamsters consisted of a diffuse hemorrhagic interstitial pneumonia at 7 days post-treatment. Lungs contained less hemorrhage and edema but increased numbers of mononuclear inflammatory cells and thickened interalveolar walls at 14 days post-treatment. A diffuse mononuclear cell infiltrate with multifocal areas of fibrosis later predominated. The protein, RNA, and DNA levels in bleomycin-treated hamsters were consistently and significantly elevated at 4 (except DNA), 7, 14, 21, and 28 days after treatment. The Ca 2+ levels in lungs of these animals at the corresponding times were increased by 158, 194, 36, 22, and 8% without any change in plasma Ca 2+. Lung soluble collagen was increased by 124, 207, 121, and 30% at 7, 14, 21, and 28 days, respectively, after bleomycin treatment. The increases in insoluble collagen were 65, 108, 132, and 91% at the corresponding times. The lung cAMP levels at 4, 7, 14, 21, and 28 days were 176, 164, 132, 158, and 96% of control, respectively, and cGMP at the corresponding times were 50, 81, 222, 198, and 137% of control. These data suggest that shifts in the intracellular levels of cAMP, cGMP, and Ca 2+ are associated with early lung changes induced by bleomycin insult and may serve as indicators to gauge the severity and progression of lung damage.