CYP3A5 is the major cytochrome P450 3A expressed in human colon and colonic cell lines

Abstract

CYP3A is known to be expressed in liver, small intestine and colon. However, its isoform distribution (CYP3A4, 3A5 and 3A7) and inducibility have not been clearly elucidated in the colon. Therefore, we analyzed CYP3A in human colon and compared its expression and inducibility to the human colonic cell lines HT29 and Caco2, which were used as models. Patients suffered either from sigmoiditis or colonic adenocarcinoma. Patients as well as HT29 and Caco2 cells were treated with rifampicin. CYP3A protein expression was analyzed in the colon of patients and in the cells by immunoblot and by isoelectric focusing enabling separation of CYP3A isoforms, while mRNA expression was determined using specific reverse transcription-polymerase chain reaction. In both human colon and cells, CYP3A5 was the main isoform expressed at the protein and mRNA levels. Rifampicin treatment had no effect on CYP3A expression. HT29 and Caco2 cells exhibiting the same CYP3A expression and inducibility might therefore be useful in vitro models for studying xenobiotic metabolism in human colon.