Species-specific expression of CYP4B1 in rabbit and human gastrointestinal tissues.
CYP4B1 is a P450 enzyme displaying tissue and species specific regulation. The rabbit CYP4B1 enzyme exhibits activity towards procarcinogenic aromatic amines. In the present study, CYP4B1 expression has been characterized in rabbit tissues using histological techniques, Northern blotting and Western blotting. Similar analyses were attempted using available human tissues. CYP4B1 mRNA and protein was demonstrated throughout the rabbit small intestine and colon. A unique 1.8 kb transcript, that is smaller than the transcript found in other tissues, was detected in rabbit stomach with a CYP4B1 specific RNA probe. No CYP4B1 protein was detected in this tissue. In rabbit liver, CYP4B1 was induced by phenobarbital primarily in zone 1 hepatocytes (periportal). In humans, CYP4B1 expression was demonstrated at low levels in human colon using in situ hybridization but not in liver or the small intestine. All rabbit gastrointestinal tissues other than stomach possess a high capacity for the activation of 2-aminofluorene compatible with CYP4B1 expression. In contrast, no activity was observed in human gastrointestinal microsomes. The present study therefore shows that CYP4B1 is an abundant P450 in the rabbit gastrointestinal tract and identifies species-specific differences in CYP4B1 expression and function.
McKinnon
R A
RA
Department of Clinical Pharmacology, Flinders University, Bedford Park, South Australia.
Burgess
W M
WM
Gonzalez
F J
FJ
Gasser
R
R
McManus
M E
ME
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004064:Digestive System / Q000201:enzymology*; D004789:Enzyme Activation; D005449:Fluorenes / Q000633:toxicity; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D009153:Mutagens / Q000633:toxicity; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D013045:Species Specificity
D005449:Fluorenes; D009153:Mutagens; D012333:RNA, Messenger; C012177:2-aminofluorene; D003577:Cytochrome P-450 Enzyme System