Dose response in 3-methylindole-induced bronchiolar epithelial necrosis in mice

The effects of increasing concentrations of 3-methylindole (3MI) on the lungs, liver, and kidneys of mice were studied. Groups of five male mice were injected intraperitoneally with 10 mg, 100 mg, 200 mg, 300 mg, 400 mg, 600 mg, or 800 mg of 3MI/kg in corn oil. A control group received corn oil only. One of five mice which received 600 mg and all five which received 800 mg 3MI/kg died between 10 and 20 hours after injection. Surviving mice were killed 24 hours after 3MI. Lungs, liver and kidneys from all mice were examined by light microscopy. Brain, heart and spleen were also examined in mice which received 400 or 600 mg 3MI/kg. Histologic changes were limited to the lungs and consisted of degeneration or necrosis of bronchiolar epithelium in all mice which received at least 100 mg 3MI/kg. Severity of bronchiolar lesions was proportional to the dose of 3MI in mice which survived for 24 hours. Epithelial necrosis in the axial bronchi accompanied bronchiolar lesions in one mouse which received 400 mg and in three of five mice which received 600 mg 3MI/kg.