In vitro 2-methoxyacetaldehyde adduct formation used for proteomic-based glycol ether biomarker development with surface enhanced laser desorption ionization (SELDI) analysis.
Toxicologist 2007 Mar; 96(1):85
The protein adduct formation of 2-Methoxyacetaldehyde (MALD, CAS 10312- 83-1) was tested as a potential biomarker of glycol ether exposure. MALD is a reactive intermediate in the metabolism of 2-methoxyethanol (2ME, CAS 109-86-4), a glycol ether known to produce reproductive effects in laboratory animals and is a potential carcinogen. Bioactivation of 2ME is reported to occur via oxidation by alcohol dehydrogenase to MALD and subsequent aldehyde dehydrogenase to methoxyacetic acid (MAA, CAS 625-45-6). Protein and DNA adducts have been reported for 2ME, and MALD has been suggested as the likely source of macromolecular adduct formation. In the current study MALD, along with 2ME and MAA were tested in vitro to evaluate adduct formation using human hemoglobin or albumin. Surface Enhanced Laser Desorption Ionization (SELDI) with Time of Flight mass spectrometry was used to detect adduct formation in 0.1 µg hemoglobin or albumin incubates. The study showed that the reactivity of MALD with albumin was several fold greater than for hemoglobin. The reaction of MALD with the alpha-globin chain was greater than that of the beta-globin portion of hemoglobin. After 3 hours the MALD-adduct levels for albumin > alpha-globin > beta-globin. The MALD adduct levels did not continued to increase further during the 24- hour test period, and no corresponding adduct formation was noted for 2ME or MAA. Tryptic digests of the proteins may be utilized for specific proteomic-based biomarkers of exposure to glycol ethers.
Cell-alteration; Cell-damage; Cellular-reactions; Cell-biology; Cell-function; Cell-metabolism; Cell-morphology; Cell-transformation; Epidemiology; Biomarkers; Blood-samples; Blood-cells; Animal-studies; Humans; In-vitro-studies
10312- 83-1; 109-86-4
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina