We performed
in vivo and
in vitro studies to determine the induction of human cytochrome P450 (CYP) using chimeric mice with humanized liver (PXB-mice
®) and human hepatocytes isolated from the PXB-mice (PXB-cells), which were derived from the same donor. For the
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We performed
in vivo and
in vitro studies to determine the induction of human cytochrome P450 (CYP) using chimeric mice with humanized liver (PXB-mice
®) and human hepatocytes isolated from the PXB-mice (PXB-cells), which were derived from the same donor. For the
in vivo study, PXB-mice were injected with 3-methylcholanthrene (3-MC, 2 or 20 mg/kg) or rifampicin (0.1 or 10 mg/kg) for four days. For the
in vitro study, PXB-cells were incubated with 3-MC (10, 50, or 250 ng/mL) or with rifampicin (5 or 25 μg/mL). The
CYP1A1 and
1A2, and
CYP3A4 mRNA expression levels increased significantly in the PXB-mouse livers with 20 mg/kg of 3-MC (
Cmax, 12.2 ng/mL), and 10 mg/kg rifampicin (
Cmax, 6.9 µg/mL), respectively. The
CYP1A1 mRNA expression level increased significantly in PXB-cells with 250 ng/mL of 3-MC, indicating lower sensitivity than
in vivo. The
CYP1A2 and
CYP3A4 mRNA expression levels increased significantly with 50 ng/mL of 3-MC, and 5 μg/mL of rifampicin, respectively, which indicated that the sensitivities were similar between
in vivo and
in vitro studies. In conclusion, PXB-mice and PXB-cells provide a robust model as an intermediate between
in vivo and
in vitro human metabolic enzyme induction studies.
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