A joint research group including Professor Kei Zaitsu of the Faculty of Biology-Oriented Science and Technology, Kindai University, Research Officer Kazuaki Hisatsune of the Forensic Science Laboratory, Aichi Prefectural Police Headquarters, Associate Professor Tomomi Asano of the College of Human Life and Environment, Kinjo Gakuin University, and Researcher Masaru Taniguchi of the Nagoya City Public Health Research Institute has successfully identified new biomarkers capable of detecting traces of cyanide poisoning with high precision. The findings were published in Archives of Toxicology.
Cyanide is an extremely toxic chemical substance that, in addition to being involved in poisoning incidents, is sometimes used in homicides and even terrorist attacks. Because cyanide targets intracellular mitochondria and inhibits cellular energy production, it causes severe, acute poisoning symptoms in a short period. Consequently, when cyanide poisoning is suspected, testing biological specimens such as blood to objectively prove its ingestion becomes indispensable. However, testing cyanide directly in the blood requires extreme care because it is chemically unstable in blood samples. To determine cyanide ingestion with higher accuracy, indirect biomarkers that signify its intake are important.
In recent years, 2-aminothiazoline-4-carboxylic acid (ATCA), which is a cyanide metabolite reported to have relatively high stability in the blood, has drawn attention as a promising new biological indicator. However, because ATCA is produced inside the body through a reaction between cyanide and cystine (which is generated from methionine, a sulfur-containing amino acid abundant in meat and eggs), its production levels can fluctuate depending on dietary intake. Furthermore, because ATCA is cleared from the body at a relatively fast rate, additional alternative biomarkers have been necessary.
The research group conducted this study to investigate whether ATCA is affected by diet and to discover new alternative biomarkers for cyanide exposure.
First, mice were fed three types of diets containing varying amounts of methionine and cystine for one week, after which they were administered a toxic dose of cyanide to examine subsequent blood ATCA concentrations and metabolic shifts. The results revealed that blood ATCA concentrations 15 and 30 minutes post-administration showed no dietary influence, proving that variations in dietary methionine and cystine do not impact ATCA production. Furthermore, a metabolomic analysis of the mice's blood serum detected 117 distinct metabolites. Utilizing information science techniques to narrow down which of these metabolites contributed most to distinguishing the cyanide-administered group from the unadministered group, the team discovered 25 compounds that serve as highly accurate new biomarkers for identifying cyanide exposure.
With continued validation using human autopsy samples, these newly identified biomarkers are expected to become practical tools in forensic science, assisting in criminal investigations involving cyanide and the precise determination of causes of death.
Journal Information
Publication: Archives of Toxicology
Title: Assessment of 2-aminothiazoline-4-carboxylic acid (ATCA) formation and identification of robust serum metabolic biomarkers for acute cyanide exposure in mice fed diets with varying methionine and cystine content
DOI: 10.1007/s00204-026-04435-7
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