Similarities in diesel exhaust particles induced alterations in expression of cytochrome P-450 and glutathione S-transferases in rat lymphocytes and lungs

Abstract

1. Freshly prepared peripheral blood lymphocytes (PBL) are known to express cytochrome P450s (CYPs) and glutathione S-transferases (GSTs) involved in the bioactivation and detoxification of organic components of diesel exhaust particles (DEPs). To validate that blood lymphocyte expression profiles could be used as a biomarker to predict exposure to vehicular emissions, similarities in the alterations in the mRNA expression of CYPs and GSTs were studied in PBL and lungs of rats exposed to DEPs.

2. Adult male Wistar rats were treated transtracheally with different doses of DEPs (3.75- or 7.5- or 15- or 30-mg/kg b.wt.). The animals were anaesthetized after 24 h and blood was drawn and lungs were taken out and processed.

3. DEP produced a similar pattern of increase in the mRNA expression of CYPs (CYP1A1, 1A2, 1B1, 2E1), associated arylhydrocarbon receptor (Ahr) and arylhydrocarbon nuclear translocator (Arnt) and GSTs (GSTPi, GSTM1 and GSTM2) at all the doses in lungs and PBL. The protein expression of CYP1A1/1A2 and 2E1 and catalytic activity of CYPs and GSTs also showed a similar pattern of increase in blood lymphocyte and in lungs isolated from DEP treated rats.

4. Our data indicating similarities in the alterations in the expression of carcinogen metabolizing CYPs and GSTs in PBL with the lung enzymes suggests the suitability of using expression profiles of blood lymphocyte CYPs and GSTs as a biomarker to predict exposure to vehicular emissions.

Keywords::

• DEP
• lungs
• lymphocytes
• expression
• CYPs
• biomarker

Acknowledgements

The authors are grateful to the Director, Indian Institute of Toxicology Research, CSIR, Lucknow for his keen interest in carrying out the study. Mr. Amit Sharma is thankful to Council of Scientific & Industrial Research (CSIR), New Delhi for providing Senior Research Fellowship. The financial support of Defence Research & Development Establishment (DRDE), Gwalior in carrying out the above studies is gratefully acknowledged. The technical assistance of Mr. B. S. Pandey is also gratefully acknowledged.

IITR Communication Number: 2926

Declaration of interest

The authors report no conflicts of interest.