Skip Navigation
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.


The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Your Environment. Your Health.

Publication Detail

Title: Role of CYP2B in Phenobarbital-Induced Hepatocyte Proliferation in Mice.

Authors: Li, Lei; Bao, Xiaochen; Zhang, Qing-Yu; Negishi, Masahiko; Ding, Xinxin

Published In Drug Metab Dispos, (2017 08)

Abstract: Phenobarbital (PB) promotes liver tumorigenesis in rodents, in part through activation of the constitutive androstane receptor (CAR) and the consequent changes in hepatic gene expression and increases in hepatocyte proliferation. A typical effect of CAR activation by PB is a marked induction of Cyp2b10 expression in the liver; the latter has been suspected to be vital for PB-induced hepatocellular proliferation. This hypothesis was tested here by using a Cyp2a(4/5)bgs-null (null) mouse model in which all Cyp2b genes are deleted. Adult male and female wild-type (WT) and null mice were treated intraperitoneally with PB at 50 mg/kg once daily for 5 successive days and tested on day 6. The liver-to-body weight ratio, an indicator of liver hypertrophy, was increased by 47% in male WT mice, but by only 22% in male Cyp2a(4/5)bgs-null mice, by the PB treatment. The fractions of bromodeoxyuridine-positive hepatocyte nuclei, assessed as a measure of the rate of hepatocyte proliferation, were also significantly lower in PB-treated male null mice compared with PB-treated male WT mice. However, whereas few proliferating hepatocytes were detected in saline-treated mice, many proliferating hepatocytes were still detected in PB-treated male null mice. In contrast, female WT mice were much less sensitive than male WT mice to PB-induced hepatocyte proliferation, and PB-treated female WT and PB-treated female null mice did not show significant difference in rates of hepatocyte proliferation. These results indicate that CYP2B induction plays a significant, but partial, role in PB-induced hepatocyte proliferation in male mice.

PubMed ID: 28546505 Exiting the NIEHS site

MeSH Terms: Animals; Aryl Hydrocarbon Hydroxylases/deficiency; Aryl Hydrocarbon Hydroxylases/genetics; Aryl Hydrocarbon Hydroxylases/physiology*; Cell Proliferation/drug effects; Cell Proliferation/physiology; Cytochrome P450 Family 2/physiology*; Enzyme Induction/drug effects; Enzyme Induction/physiology; Female; Hepatocytes/drug effects*; Hepatocytes/enzymology*; Hypnotics and Sedatives/pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phenobarbital/pharmacology*; Steroid Hydroxylases/deficiency; Steroid Hydroxylases/genetics; Steroid Hydroxylases/physiology*

to Top