| Global Gene Expression Profiling in Whole-Blood Samples from Individuals Exposed to Metal Fumes Zhaoxi Wang,1 Donna Neuburg,2 Cheng Li,2 Li Su,1 Jee Young Kim,1 Jiu Chiuan Chen,1 and David C. Christiani1,3 1Department of Environmental Health, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts, USA; 2Department of Statistical Sciences, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA; 3Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA Abstract
Accumulating evidence demonstrates that particulate air pollutants can cause both pulmonary and airway inflammation. However, few data show that particulates can induce systemic inflammatory responses. We conducted an exploratory study using microarray techniques to analyze whole-blood total RNA in boilermakers before and after occupational exposure to metal fumes. A self-controlled study design was used to overcome the problems of larger between-individual variation interferences with observations of relatively smaller changes caused by environmental exposure. Moreover, we incorporated the dichotomous data of absolute gene expression status in the microarray analyses. Compared with nonexposed controls, we observed that genes with altered expression in response to particulate exposure were clustered in biologic processes related to inflammatory response, oxidative stress, intracellular signal transduction, cell cycle, and programmed cell death. In particular, the preinflammatory cytokine interleukin 8 and one of its receptors, chemokine receptor 4, seemed to play important roles in early-stage response to heavy metal exposure and were down-regulated. Furthermore, most observed expression variations were from nonsmoking exposed individuals, suggesting that smoking profoundly affects whole-blood expression profiles. Our study is the first to demonstrate that with a paired sampling study design of pre- and postexposed individuals, small changes in gene expression profiling can be measured in whole-blood total RNA from a population-based study. This technique can be applied to evaluate the host response to other forms of environmental exposures. Key words: functional pathway, gene expression profiling, inflammation, occupational particulate exposure, whole-blood total RNA. Environ Health Perspect 113:233-241 (2005) . doi:10.1289/txg.7273 available via http://dx.doi.org/ [Online 22 November 2004]
Address correspondence to D. Christiani, 665 Huntington Ave., I-1402, Boston, MA 02115 USA. Telephone: (617) 432-3323. Fax: (617) 432-3441. E-mail: dchristi@hsph.harvard.edu This work was supported by grant T32 ES07069 from the National Institute of Environmental Health Sciences and by research grants ES009860, CA074386, CA090578, and CA092824 from the National Institutes of Health. The authors declare they have no competing financial interests.
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