SPECIES-SPECIFIC EXPRESSION OF CYP4B1 IN RABBIT AND HUMAN GASTROINTESTINAL TISSUES

CYP4B1 is a P450 enzyme displaying tissue and species specific regulat ion. The rabbit CYP4B1 enzyme exhibits activity towards procarcinogeni c aromatic amines. In the present study, CYP4B1 expression has been ch aracterized in rabbit tissues using histological techniques, Northern blotting and Western blotting. Similar analyses were attempted using a vailable human tissues. CYP4B1 mRNA and protein was demonstrated throu ghout the rabbit small intestine and colon. A unique 1.8 kb transcript , that is smaller than the transcript found in other tissues, was dete cted in rabbit stomach with a CYP4B1 specific RNA probe. No CYP4B1 pro tein was detected in this tissue. In rabbit liver, CYP4B1 was induced by phenobarbital primarily in zone 1 hepatocytes (periportal). In huma ns, CYP4B1 expression was demonstrated at low levels in human colon us ing in situ hybridization but not in liver or the small intestine. All rabbit gastrointestinal tissues other than stomach possess a high cap acity for the activation of 2-aminofluorene compatible with CYP4B1 exp ression. In contrast, no activity was observed in human gastrointestin al microsomes. The present study therefore shows that CYP4B1 is an abu ndant P450 in the rabbit gastrointestinal tract and identifies species -specific differences in CYP4B1 expression and function.