Effects of Subchronic Exposures to Concentrated Ambient Particles in Mice: VI. Gene Expression in Heart and Lung Tissue

The purpose of this exploratory study within the integrated subchronic inhalation exposure study (Lippmann et al., 2005) was to identify genes in heart and lung tissue that changed in expression level as a result of subchronic exposure to concentrated ambient particles (CAPs). Identification of CAPs exposure-related changes in gene expression could serve in the formulation of mechanistic hypotheses and/or to suggest possible biomarkers of exposure. In this exploratory study undertaken here, tissues from multiple replicates of ApoE/low-density-lipoprotein double knockout (DK) mice were examined for relative exposure-related changes in gene expression. Due to limited resources, the number of replicates was three for each tissue (lung and heart) of each exposure condition (CAPs or air control). A rigorous comparison of exposure versus control data using the "significance analysis of microarrays" (SAM) method indicated that only one gene was differentially expressed at a significant level. However, when using a less restrictive, nonstatistical analytical treatment of the data, several genes that might be involved in PM-related heart or lung pathology, and/or the circadian rhythm of physiological processes, were identified. A more comprehensive study is required to mre definitively assess differences in gene expression in heart and lung resulting from exposure to CAPs.