Cytochrome P450 2A isoenzymes in freshly prepared blood lymphocytes isolated from rats and validation as a biomarker for clinical studies in humans

Abstract

1. The present study aimed to identify the expression of carcinogen metabolizing cytochrome P4502A (CYP2A) isoenzymes in freshly prepared rat peripheral blood lymphocytes (PBL) isolated from adult rats and investigate similarities in the regulation of lymphocyte CYP2A-isoenzymes with the tissue enzyme.

2. qRT-PCR studies demonstrated significant constitutive mRNA expression of CYP2A-isoenzymes in PBL isolated from male and female rats which further increases significantly after pretreatment with nicotine or 3-methylcholanthrene (MC) indicating responsiveness of CYP2A-isoenzymes in PBL. This increase in the CYP2A expression was associated with an increase in the protein expression and CYP2A3-dependent coumarin hydroxylase (COH) activity in PBL.

3. Clinical studies further demonstrated significant increase in the expression of CYP2A6 and associated enzyme activity in PBL isolated from lung cancer patients. Our data thus provided evidence for similarities in the regulation of carcinogen metabolizing CYP2A-isoenzymes in PBL with the tissue enzymes. Further, responsiveness of blood CYP2A6 in human blood lymphocytes isolated from lung cancer patients has led us to suggest that associating expression profiles of CYP2A6 and other polycyclic aromatic hydrocarbons (PAH)-responsive CYPs in PBL with the genotyping data could lead to the development of a possible screen to monitor and predict environment-induced diseases and toxicity in humans.

Keywords::

• CYP2A
• mRNA
• protein
• biomarker
• lung cancer

Acknowledgments

The authors are grateful to the Director, Indian Institute of Toxicology Research (Council of Scientific & Industrial Research, CSIR), Lucknow for his keen interest and support in carrying out the study. Mr. Amit Sharma is thankful to CSIR, New Delhi for providing a Senior Research Fellowship. The financial assistance of Indo-US project on Fingerprints of blood Cytochrome P450s: Biomarker of exposure and effect sponsored by ICMR, New Delhi, for carrying out the above study is gratefully acknowledged. The technical assistance of Mr. B. S. Pandey is also appreciatively acknowledged. IITR communication number 3031.

Declaration of interest

The authors report no declaration of interest.