CORRELATION BETWEEN PULMONARY CYTOCHROME-P450 TRANSCRIPTS AND THE ORGAN-SELECTIVE PNEUMOTOXICITY OF 3-METHYLINDOLE

3-Methylindole (3MI) is a species- and organ-selective pneumotoxin; go ats are the most susceptible species, mice are intermediate in suscept ibility, and rabbits are the least susceptible species to its toxicity . Four different cDNA probes representative of human cytochrome P450 g enes CYP2F1, CYP4B1, CYP2A6, and CYP2B6 were hybridized against RNA fr om lung and liver tissues of goat, mouse and rabbit. Transcripts repre sentative of pulmonary P450s CYP2F1, CYP4B] and CYP2B6 were present in goat lung. Transcripts for the CYP2F1 and CYP4B1 genes were observed in rabbit and mouse lung. In general, the probes selectively hybridize d to pulmonary but not hepatic transcripts of all three species. The d ifferences in susceptibilities among the three species could not be ex plained by the lack of 4B1 and 2F1 transcripts in the lungs of mice or rabbits that are less susceptible than goats, but the selective expre ssion in the lung tissues of all three species may participate in the organ-selective bio-activation and pulmonary toxicity of 3MI in these species.