Genomic analysis of the rat lung following elemental mercury vapor exposure

Elemental mercury (Hg-0) is a highly toxic chemical with increasing public health concern. Although the lung receives the highest exposure to Hg-0 vapor, it is resistant to Hg-0 toxicity relative to the kidney and brain. In an earlier study, exposure of rats to 4 mg Hg-0 vapor/m(3), 2 h per day for 10 days, did not produce pathological alterations in the lung but increased metallothionein and glutathione S-transferase in the kidney. This study was undertaken to examine pulmonary gene expression associated with Hg-0 vapor inhalation. Total RNA was extracted from lung tissues of rats, previously exposed to air or Hg-0 vapor, and subjected to microarray analysis. Hg-0 vapor exposure increased the expression of genes encoding inflammatory responses, such as chemokines, tumor necrosis factor-alpha (TNFalpha), TNF-receptor-1, interleukin-2 (IL-2), IL-7, prostaglandin E2 receptor, and heat-shock proteins. As adaptive responses, glutathione S-transferases (GST-pi, mGST1), metallothionein, and thioredoxin peroxidase were all increased in response to Hg exposure. Some transporters, such as multidrug resistance-associated protein (MRP), P-glycoprotein, and zinc transporter ZnT1, were also increased in an attempt to reduce pulmonary Hg load. The expression of transcription factor c-jun/AP-1 and PI3-kinases was suppressed, while the expression of protein kinase-C was increased. Expression of epidermal fatty acid-binding protein was also enhanced. Real-time RT-PCR and Western blot analyses confirmed the microarray results. In summary, genomic analysis revealed an array of gene alterations in response to Hg-0 vapor exposure, which could be important for the development of pulmonary adaptation to Hg during Hg-0 vapor inhalation.