Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 51, 2021 - Issue 3
521
Views
28
CrossRef citations to date
0
Altmetric
General Xenobiochemistry

Expression of cytochrome P450 isozyme transcripts and activities in human livers

ORCID Icon, ORCID Icon, ORCID Icon &
Pages 279-286 | Received 13 Nov 2020, Accepted 19 Dec 2020, Published online: 28 Dec 2020
 

Abstract

  1. Individual differences in cytochrome P450 (CYP) enzymes contribute to responses to drugs and environmental chemicals. The expression of CYPs is influenced by sex, age, and ethnicity. Human CYP studies are often conducted with human liver microsomes and liver cells to evaluate chemical induction and drug interactions. However, the basal or constitutive expression of CYP transcripts and enzyme activities in the intact liver are also important in our understanding of individual variation in CYPs.

  2. This study utilised 100 human liver samples to profile the constitutive expression of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 4A11 enzyme activity and transcript levels. The mRNA expression of the CYPs and xenobiotic receptors AhR, CAR, and PXR was examined via qPCR.

  3. Results showed that there was greater inter-individual variation in mRNA expression than in enzyme activities, except for CYP2C19. Females had higher CYP3A4 activity than males. Children had lower CYP4A14 activity, while elderly had lower P450 oxidoreductase activity. Compared to Caucasians, Hispanics had higher CYP2C8 activity and higher CYP2B6, CYP2C9, and CYP2C19 mRNA expression, whereas African Americans had lower CYP2D6 mRNA expression.

  4. These results add to our understanding of individual variations in xenobiotic metabolism and toxicology.

Acknowledgements

The authors thank Drs. Andrew Parkinson, David B. Buckley, and Ronnie L. Yeager for their contributions to this work. The authors thank Drs. Mike Hughes and Janice Lee for critical in-house review of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

The information in this document has been subjected to review by the Centre for Computational Toxicology and Exposure and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.

Additional information

Funding

This study was supported by NIH Research Grant ES-013714, ES-09716, ES-009649, DK-081461, RR-021940, and NIH Training Grant ES-07079.

Log in via your institution

Log in to Taylor & Francis Online

PDF download + Online access

  • 48 hours access to article PDF & online version
  • Article PDF can be downloaded
  • Article PDF can be printed
USD 65.00 Add to cart

Issue Purchase

  • 30 days online access to complete issue
  • Article PDFs can be downloaded
  • Article PDFs can be printed
USD 897.00 Add to cart

* Local tax will be added as applicable

Related Research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.