Marmoset pulmonary cytochrome P450 2F1 oxidizes biphenyl and 7-ethoxycoumarin and hepatic human P450 substrates

Abstract

1. A potentially useful animal model for preclinical studies is the common marmoset (Callithrix jacchus). In this study, using reverse-transcription polymerase chain reaction from marmoset livers, we identified a novel cytochrome P450 (P450) 2F1 cDNA with an open reading frame of 1473 bp.

2. High sequence identities of 92-94% with primate P450 2 F amino acid sequences were indicated by deduced amino acid sequences of P450 2F1 cDNA. Phylogenetic analysis indicates that marmoset P450 2F1 is more congruent with primate P450 2 F forms than those of other species such as rodents.

3. Among five tissue types examined, abundant expression of marmoset P450 2F1 mRNA and P450 2F1 protein in lungs was shown. Cynomolgus monkey P450 2F1 mRNA was abundantly expressed in lungs as well as testes and ovaries in 10 tissue types.

4. Similar to those of humans and cynomolgus monkeys, marmoset P450 2F1 heterologously expressed in Escherichia coli membranes efficiently catalyzed 7-ethoxycoumarin O-deethylation and biphenyl hydroxylation, however unlike human P450 2F1, marmoset P450 2F1 exhibited hydroxylation activity toward coumarin and chlorzoxazone.

5. These findings indicated that P450 2F1 enzyme expressed in marmoset lungs and also catalyzed metabolism of xenobiotics, suggesting the importance of P450 2 F-dependent drug metabolism in marmoset lungs.

• Common marmoset
• CYP2F1
• drug oxidation

Acknowledgements

The authors thank Drs Elizabeth Gillam, Makiko Shimizu and Norie Murayama for their technical help and Mr Lance Bell for his advice on English writing.

Declaration of interest

This work resulted from the “Construction of System for Spread of Primate Model Animals” initiative under the Strategic Research Program for Brain Sciences of the Japan Agency for Medical Research and Development. Shotaro Uehara was also supported partly by the Japan Society for the Promotion of Science Grant-in-Aid for Young Scientists B [17K15520]. The authors alone are responsible for the content and for writing the article and report no declarations of interest.