Abstract
Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this study, we aimed to identify, validate, and characterize the mRNA biomarker that can detect the exposure of sodium cyanide. To identify reliable biomarkers for sodium cyanide exposure, critical criteria were defined for candidate selection: (1) the expression level of mRNA significantly changes in response to sodium thiocyanate treatment in transcriptomics results (fold change > 2.0 or <0.50, adjusted p-value < 0.05); and (2) the mRNA level is significantly modulated by sodium cyanide exposure in both normal human lung cells and rat lung tissue. We identified the following mRNA biomarker candidates: ADCY5, ANGPTL4, CCNG2, CD9, COL1A2, DACT3, GGCX, GRB14, H1F0, HSPA1A, MAF, MAT2A, PPP1R10, and PPP4C. The expression levels of these candidates were commonly downregulated by sodium cyanide exposure both in vitro and in vivo. We functionally characterized the biomarkers and established the impact of sodium cyanide on transcriptomic profiles using in silico approaches. Our results suggest that the biomarkers may contribute to the regulation and degradation of the extracellular matrix, leading to a negative effect on surrounding lung cells.
Highlights
Hazardous substances, whether artificially made or naturally occurring, can enter the human body through the main routes of exposure such as inhalation, ingestion, and dermal contact, and cause various effects on health [1]
Once exposed to hazardous substances, it is important to measure the degree of exposure [3,4]
Biomarkers in exposure assessment refer to actual chemicals, chemical metabolites, or changes in organic matter in the body that indicates the exposure of an organism to a chemical [7]
Summary
Whether artificially made or naturally occurring, can enter the human body through the main routes of exposure such as inhalation, ingestion, and dermal contact, and cause various effects on health [1]. Human biomonitoring uses biomarkers to assess specific exposures and to predict the risk of adverse health effects in individuals and populations [5,6]. Three types of biomarkers are used when dealing with exposure assessments; biomarkers of susceptibility, biomarkers of exposure, and biomarkers of effect [8,9,10] They can identify whether the exposure has occurred, and the route, toxic pathway, and effects of the exposure. The direct method for assessing exposure to chemicals is to analyze the actual chemicals or their metabolites in blood and urine specimens [13]. This method has limitations in its application to chemicals that are rapidly metabolized and eliminated from the body [14]. When a chemical incident occurs, it is difficult to measure exposure and risk assessment a few days after the chemical incident
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