Correlation between pulmonary cytochrome P450 transcripts and the organ-selective pneumotoxicity of 3-methylindole.
3-Methylindole (3MI) is a species- and organ-selective pneumotoxin; goats are the most susceptible species, mice are intermediate in susceptibility, and rabbits are the least susceptible species to its toxicity. Four different cDNA probes representative of human cytochrome P450 genes CYP2F1, CYP4B1, CYP2A6, and CYP2B6 were hybridized against RNA from lung and liver tissues of goat, mouse and rabbit. Transcripts representative of pulmonary P450s CYP2F1, CYP4B1 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 hybridized to pulmonary but not hepatic transcripts of all three species. The differences in susceptibilities among the three species could not be explained by the lack of 4B1 and 2F1 transcripts in the lungs of mice or rabbits that are less susceptible than goats, but the selective expression in the lung tissues of all three species may participate in the organ-selective bioactivation and pulmonary toxicity of 3MI in these species.
Ramakanth
S
S
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Thornton-Manning
J R
JR
Wang
H
H
Maxwell
H
H
Yost
G S
GS
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D015152:Blotting, Northern; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D015342:DNA Probes; D006041:Goats; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D012862:Skatole / Q000633:toxicity*; D013045:Species Specificity; D014158:Transcription, Genetic / Q000187:drug effects
D015342:DNA Probes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D012862:Skatole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6