Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers.

Author(s): Peretz A, Peck EC, Bammler TK, Beyer RP, Sullivan JH, Trenga CA, Srinouanprachnah S, Farin FM, Kaufman JD

Affiliation(s): Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, Washington, USA.

Publication date & source: 2007-11, Inhal Toxicol., 19(14):1107-19.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.

Ambient fine particulate matter has been associated with cardiovascular and other diseases in epidemiological studies, and diesel exhaust (DE) is a major source of urban fine particulate matter. Air pollution's cardiovascular effects have been attributed to oxidative stress and systemic inflammation, with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. We conducted a pilot study using microarray techniques to analyze whether global gene expression profiles in peripheral blood mononuclear cells (PBMCs) can elucidate effects of DE inhalation, for further investigation of mechanisms underlying vascular effects. In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in 2-h sessions. We isolated RNA (Trizol/Qiagen method) from PBMCs before and two times after each exposure. RNA samples were arrayed using the Affymetrix U133 Plus 2.0 arrays. Microarray analyses were conducted on five subjects with available RNA samples from exposures to FA and to the highest DE inhalation (200 microg/m(3) of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets evidenced differential expression (more than 1.5-fold up- or downregulated with p < .05) between FA and DE exposure. These genes demonstrated a clear distinction between the FA and DE groups and an indication of a time-dependent effect on biological processes such as inflammation and oxidative stress. This study addresses the value of using PBMC gene expression to assess pathways relevant to cardiovascular effect in healthy individuals.