| Identification of Gene Markers for Formaldehyde Exposure in Humans Guang-Yong Li,1 Hye-Young Lee,1 Ho-Sang Shin,2 Hyeon-Young Kim,3 Cheol-Hong Lim,3 and Byung-Hoon Lee1 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 2Department of Environmental Education and Abuse Drug Research Center, Kongju National University, Kongju, Republic of Korea; 3Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency, Daejeon, Republic of Korea Abstract
Background: Formaldehyde (FA) is classified as a human carcinogen and has been linked to increased leukemia rates in some epidemiologic studies. Inhalation of FA induces sensory irritation at relatively low concentrations. However, little is known concerning the cellular alterations observed after FA exposure in humans. Objectives: Our aim was to profile global gene expression in Hs 680.Tr human tracheal fibroblasts exposed to FA and to develop biomarkers for the evaluation of FA exposure in humans. Methods and Results: We used gene expression analysis, and identified 54 genes designated as FA responsive. On the basis of these data, we conducted an exploratory analysis of the expression of these genes in human subjects exposed to high or low levels of FA. We monitored FA exposure by measuring the urinary concentration of thiazolidine-4-carboxylate (TZCA) , a stable and quantitative cysteinyl adduct of FA. Nine genes were selected for real-time PCR analysis ; of these, BHLHB2, CCNL1, SE20-4, C8FW, PLK2, and SGK showed elevated expression in subjects with high concentrations of TZCA. Conclusion: The identification of gene marker candidates in vitro using microarray analysis and their validation using human samples obtained from exposed subjects is a good tool for discovering genes of potential mechanistic interest and biomarkers of exposure. Thus, these genes are differentially expressed in response to FA and are potential effect biomarkers of FA exposure. Key words: biomarker, carcinogenesis, formaldehyde, human study, microarray, toxicogenomics. Environ Health Perspect 115:1460–1466 (2007) . doi:10.1289/ehp.10180 available via http://dx.doi.org/ [Online 12 July 2007]
Address correspondence to B-H. Lee, College of Pharmacy, Seoul National University, San 56-1, Sillim-dong, Gwanak-gu, Seoul 151-742, Republic of Korea. Telephone: +82-2-880-7843. Fax: +82-2-874-7843. E-mail: lee@snu.ac.kr Supplemental Material is available online (http://www.ehponline.org/docs/2007/10180/suppl.pdf) . This work was supported by the Ministry of Environment as "The Eco-Technopia 21 Project." The authors declare they have no competing financial interests. Received 20 February 2007 ; accepted 12 July 2007.
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