Gene expression profiling of candidate genes in peripheral blood mononuclear cells for predicting toxicity of diesel exhaust particles

Abstract

To validate gene expression profiling of peripheral blood mononuclear cells (PBMCs) as a surrogate for monitoring tissue expression, this study using RT-PCR-based TaqMan low-density array (TLDA) was initiated to investigate similarities in the mRNA expression of target genes altered by exposure to diesel exhaust particles (DEPs) in freshly prepared PBMCs and in lungs. Adult Wistar rats were treated transtracheally with a single dose of 7.5 or 15 or 30mg/kg DEPs and sacrificed 24h later. Blood and lungs were immediately taken out and processed for RT-PCR. DEP treatment induced similar patterns of increase in the expression of polycyclic aromatic hydrocarbon-responsive cytochrome P450s, the phase II enzymes, and their associated transcription factors in both lungs and PBMCs, at all doses. Similar to that seen in lungs, a dose-dependent increase was observed in the expression of genes involved in inflammation, such as cytokines, chemokines, and adhesion molecules, in PBMCs. The expression of various genes involved in DNA repair and apoptosis was also increased in a dose-dependent manner in PBMCs and lungs. The present TLDA data indicating similarities in the responsiveness of candidate genes involved in the toxicity of DEPs between PBMCs and lungs after exposure to DEPs demonstrate that expression profiles of genes in PBMCs could be used as a surrogate for monitoring the acute toxicity of fine and ultrafine particulate matter present in vehicular emissions.