Gene Expression Pattern in Spontaneously Hypertensive Rats Exposed to Urban Particulate Matter (EHC-93)

Abstract

Epidemiological studies show associations of short-term exposure to particulate matter with morbidity and mortality. Although many studies investigate the health effects of ambient particulate matter, the associated mechanisms, and the causality, they often focus on classical parameters. The objective of the present study was to gain insight into the roles of a wide range of genes in this process. Particular attention has been paid to immediate oxidative stress in the lung. We isolated total lung RNA from spontaneously hypertensive male rats 2–40 h after exposure to reference EHC-93 (10 mg/kg). Our results show that exposure to particulate matter generates a time-dependent pattern of gene expression. From the 8799 genes or expressed sequence tags tested, we see that 132 genes were up- or downregulated shortly after exposure (i.e., 2–6 h), whereas after 15–21 h and 24–40 h, 46 and 56 genes showed altered expression, respectively. Focusing on the earliest point, 99 of the 132 genes were identified as unique. They include genes involved in an oxidative stress response (hemeoxygenase-1, metallothioneins, and thioredoxin reductase), an inflammatory response macrophage inflammatory protein-2, and tumor necrosis factor α), transcription factors belonging to the activating protein-1 family, and genes involved in cardiovascular functions. The present study, although not representing an ambient situation, is used to identify the biological pathways implicated in the initial injury response to PM exposure. Using Affymetrix chips, this study shows time-dependent gene expression, it identifies many genes that can be affected by exposure to particulate matter, and it confirms the involvement of oxidative stress in particulate-matter-related effects.