Tissue and subcellular distribution and excretion of 3-[14C]methylindole in rabbits after intratracheal infusion.

The tissue and subcellular distribution and urinary excretion pattern of radioactivity in rabbits after intratracheal administration of a 14C-labeled pulmonary toxin, 3-methylindole (3MI), was studied. Approximately 40% of the administered radioactivity appeared in the urine within 1 h but none of the radioactivity in the urine was 3MI. The lung had a higher concentration of radioactivity than the liver. Other tissues with significant radioactivity were bile, fat, kidney, and plasma. Liver had the highest total content of radioactivity due to the size of the organ. More than 80% of the total radioactivity per gram of tissue was concentrated in the nuclear and microsomal fractions of lung whereas the soluble cell fraction of liver and kidney contained approximately 60% of the radioactivity. The mitochondrial fraction in lung, liver, and kidney was consistently low in radioactivity. The lung contained significantly more residual radioactivity 4 h after dosing compared with other tissues and the elevated radioactivity persisted for 3 days. The study indicated that [14C]3MI is rapidly absorbed from the lung tissue and metabolized by the animal before being excreted in the urine. The accumulation of radioactivity in lung microsomes may be related to the metabolism of 3MI.