Formaldehyde (FA) is known as a low molecule weight organic compound and one of major components that causes
sick building syndrome (SBS), and it has been reported that FA has cytotoxic, hemotoxic, immunotoxic, and genotoxic properties. The International Agency for Research on
Cancer (IARC) has characterized FA as a
carcinogen. In this study, we investigated the effects of FA on rat
plasma proteins by using proteomic approach. Rats were exposed to three different concentrations of FA (0, 5, 10 ppm) for 2 weeks at 6 hours/day and 5 days/week in an inhalation chamber.
Malondialdehyde (MDA) assay and carbonyl spectrometric assay were conducted to determine lipid peroxidation and
protein oxidation levels and Comet assays were used for genotoxicity evaluation. Level of MDA, carbonyl insertion and DNA damage in plasma, livers, and in the lymphocytes of rats exposed to FA were found to be dose dependently increased. Proteomic analysis using three different pI ranges (3.5-5.6, 5.3-6.9, 6-9) and large size two-dimensional gel electrophoresis (2-DE) showed the presence of 3491
protein spots. A total of 32 (19 up- and 13 down-regulated)
proteins were identified as
biomarkers of FA, all showed dose dependent expressions in the plasma of rats exposed to FA and of these, 27
protein spots were identified by MALDI-TOF/MS. Several differentiated
protein groups were found.
Proteins involved in apoptosis, transportation, signaling, energy metabolism, and cell structure and motility were found to be up- or down-regulated. Among these, the identities of SNAP 23,
apolipoprotein A-1 and E,
clusterin,
kinesin, and
fibrinogen gamma were confirmed by Western blot assay, and
apo E was further analyzed by using 2-DE immunoblot assays to determine
isoform patterns. Two
cytokine including
IL4 and INF-gamma were measured in plasma with respect to
fibrinogen gamma changes. In summary, cytotoxicity, and genotoxicity assays, namely MDA lipid peroxidation assay, the carbonyl
protein oxidation assay, and Comet genotoxic assay showed that these effects increased on increasing FA levels. Proteomic analysis with three different pI ranges and long size 2-DE gel electrophoresis showed that 32
protein spots were up-or down-regulated. Of these 32
proteins, 7
proteins were confirmed by western blot assay. They could be potential
biomarkers for human diseases associated with FA exposure.