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ToxSci Advance Access published online on April 13, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi168
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Published by Oxford University Press 2005.
Received August 3, 2004
Accepted April 1, 2005

Environmental Toxicology

Differential gene expression in human peripheral blood mononuclear cells induced by cigarette smoke and its constituents

Danitsja M. van Leeuwen 1, Ralph W.H. Gottschalk 1, Marcel H. van Herwijnen 1, Edwin J. Moonen 1, Jos C.S. Kleinjans 1, and Joost H.M. van Delft 1*

1 Department of Health Risk Analysis and Toxicology, Maastricht University, PO Box 616, 6200 MD Maastricht, the Netherlands

* To whom correspondence should be addressed.
Joost H.M. van Delft, E-mail: J.vanDelft{at}GRAT.unimaas.nl


  Abstract

Currently, in molecular epidemiology studies, a wide range of methods is used to monitor early biological effects after exposure to xenobiotic agents. Gene expression profiling is considered a promising tool that may provide more sensitive, mechanism-based biomarkers. As a first step to obtain information on possible applicability of gene expression profiles as a biomarker for early biological effects due to carcinogen exposure, we conducted in vitro studies on human peripheral blood mononuclear cells (PBMC) using cigarette smoke condensate (CSC) and a selection of its genotoxic constituents as model agents, using cDNA microarray technology to investigate modulated gene expressions. In independent experiments using cells from several donors, quiescent PBMC were exposed for 18 hours followed by gene expression analyses on a microarray containing 600 toxicologically relevant genes. The search for candidate biomarker genes was binomial: first for genes similarly responding to all agents, second for agent-specific genes. Many genes were significantly deregulated by all compounds, but as the direction of deregulation frequently differed per agent, they are not useful as generic biomarker. CSC modulated the expression of many more genes than any of its constituents, with the largest effect in SERPINB2. The affected genes are involved in immune or stress response, but surprisingly no genes involved in DNA damage response were modulated, and only a few in DNA repair. In conclusion, several genes have been identified which may be potential biomarkers for population studies on early biological effects caused by cigarette smoke exposure, but no genes that represent a generic biomarker.

Keywords: Gene expression profiling; cDNA microarray; peripheral blood mononuclear cells; cigarette smoke; biomarker early effect.
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