Suggestions for applications of toxicogenomic approaches in the adverse outcome pathway of 2,4-dinitrotoluene

Kim, Hyun Soo; Yang, Jun; Kang, Doo Seok; Kee, Nam Gook; Lee, Cheol Min; Jung, Jong-Hyeon; Ahn, Yeon-Soon; Seo, Young Rok

doi:10.1007/s13530-020-00054-6

Cited by 2 publications

(1 citation statement)

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“…Considering these points, the significance of our toxicogenomic approach is that it can identify the respiratory effects of inhaled toxicants, serve as an early predictive alarm before serious lung diseases occur, and provide the possibility for identified genes to be used as biomarkers for clinical diagnosis and therapy. In addition, our results will contribute to improving the understanding of the toxic mechanism of formaldehyde, such as the construction of an adverse outcome pathway: suggestion of putative key events or adverse outcomes at diverse molecular levels, based on canonical pathways, cell processes, and diseases; inference of causal interaction; predictive assessment of carcinogenicity 67 , 68 .…”

Section: Discussionmentioning

confidence: 99%

Network-based integrated analysis for toxic effects of high-concentration formaldehyde inhalation exposure through the toxicogenomic approach

Kang

Lee

Shin

et al. 2022

Sci Rep

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Formaldehyde is a colorless, pungent, highly reactive, and toxic environmental pollutant used in various industries and products. Inhaled formaldehyde is a human and animal carcinogen that causes genotoxicity, such as reactive oxygen species formation and DNA damage. This study aimed to identify the toxic effects of inhaled formaldehyde through an integrated toxicogenomic approach utilizing database information. Microarray datasets (GSE7002 and GSE23179) were collected from the Gene Expression Omnibus database, and differentially expressed genes were identified. The network analyses led to the construction of the respiratory system-related biological network associated with formaldehyde exposure, and six upregulated hub genes (AREG, CXCL2, HMOX1, PLAUR, PTGS2, and TIMP1) were identified. The expression levels of these genes were verified via qRT-PCR in 3D reconstructed human airway tissues exposed to aerosolized formaldehyde. Furthermore, NRARP was newly found as a potential gene associated with the respiratory and carcinogenic effects of formaldehyde by comparison with human in vivo and in vitro formaldehyde-exposure data. This study improves the understanding of the toxic mechanism of formaldehyde and suggests a more applicable analytic pipeline for predicting the toxic effects of inhaled toxicants.

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Section: Discussionmentioning

confidence: 99%