PT  - JOURNAL ARTICLE
AU  - Masaru Tsutsui
AU  - Shinichiro Ogawa
AU  - Yoichi Inada
AU  - Eisuke Tomioka
AU  - Akiko Kamiyoshi
AU  - Satoru Tanaka
AU  - Tomoyuki Kishida
AU  - Masahiko Nishiyama
AU  - Makoto Murakami
AU  - Junji Kuroda
AU  - Yasuhiko Hashikura
AU  - Shinichi Miyagawa
AU  - Fumiyasu Satoh
AU  - Nobuo Shibata
AU  - Yoh-ichi Tagawa
TI  - CHARACTERIZATION OF CYTOCHROME P450 EXPRESSION IN MURINE EMBRYONIC STEM CELL-DERIVED HEPATIC TISSUE SYSTEM
AID  - 10.1124/dmd.105.007674
DP  - 2006 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 696--701
VI  - 34
IP  - 4
4099  - http://dmd.aspetjournals.org/content/34/4/696.short
4100  - http://dmd.aspetjournals.org/content/34/4/696.full
SO  - Drug Metab Dispos2006 Apr 01; 34
AB  - An in vitro system for liver organogenesis from murine embryonic stem (ES) cells has been recently established. This system is expected to be applied to the development of a new drug metabolism assay system that uses ES cells as a substitute for animal experiments. The objective of this study was to elucidate the drug metabolism profiles of the murine ES cell-derived hepatic tissue system compared with those of primary cultures of murine adult and fetal hepatocytes. The expression of the genes of the cytochrome P450 (P450) family, such as Cyp2a5, Cyp2b10, Cyp2c29, Cyp2d9, Cyp3a11, and Cyp7a1, was observed in the murine ES cell-derived hepatic tissue system at 16 days and 18 days after plating (A16 and A18). To investigate the activities of these P450 family enzymes in the murine ES cell-derived hepatic tissue system at A16 and A18, testosterone metabolism in this system was analyzed. Testosterone was hydroxylated to 6β-hydroxytestosterone (6β-OHT), 16α-OHT, 2α-OHT, and 2β-OHT in this system, and was not hydroxylated to 15α-OHT, 7α-OHT, and 16β-OHT. This metabolism profile was similar to that of fetal hepatocytes and different from that of adult hepatocytes. Furthermore, pretreatment with phenobarbital resulted in a 2.5- and 2.6-fold increase in the production of 6β-OHT and 16β-OHT. Thus, evidence for drug metabolic activities in relation to P450s has been demonstrated in this system. These results in this system would be a stepping stone of the research on the development and differentiation to adult liver. The American Society for Pharmacology and Experimental Therapeutics