Global gene expression profiling in whole-blood samples from individuals exposed to metal fumes.
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.
Wang
Zhaoxi
Z
Department of Environmental Health, Occupational Health Program, Harvard School of Public Health, Boston, Massachusetts, USA.
Neuburg
Donna
D
Li
Cheng
C
Su
Li
L
Kim
Jee Young
JY
Chen
Jiu Chiuan
JC
Christiani
David C
DC
D000328:Adult; D000395:Air Pollutants, Occupational / Q000032:analysis; D017209:Apoptosis; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D008297:Male; D008670:Metals / Q000032:analysis; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D010316:Particle Size; D010710:Phosphates / Q000378:metabolism; D012313:RNA / Q000097:blood* / Q000235:genetics; D014896:Welding
D000395:Air Pollutants, Occupational; D008670:Metals; D010710:Phosphates; D012313:RNA