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抗がん剤の毒性評価に向けた炎症マーカーS100A8/A9の可能性と代謝物マーカーの探索
Anti-cancer agents can cause various side effects, including tissue damage/inflammatory reaction. The drug-responsive biomarker analysis is essential for toxic evaluation in disease processes. S100 calcium-binding proteins A8/A9 (S100A8/A9) are highly expressed in neutrophils and monocytes/macrophages accumulated at inflammatory sites and known to be related to tissue damage and inflammation, but their response to drug toxicity has not been reported. Here we investigated the effect of anti-cancer agents (doxorubicin, cisplatin, and docetaxel) on S100A8/A9 gene expression profiles from the four representative tissues (heart, kidney, liver, and lung) in C57BL/6J mice. Both S100A8 and S100A9 expressions were elevated in all tested tissues in response to the intraperitoneal dosing of the three anti-cancer agents under toxicity-inducing conditions, and their expression patterns differ among agents/tissues. This result suggests that S100A8/A9 are useful for evaluating anti-cancer agent-induced tissue damages. Metabolomic analysis also revealed that some metabolites showed similar temporal patterns with S100A8/A9 expression. Although there were no metabolites having a common temporal trend among the three agents, the amounts of fumarate (doxorubicin-treated heart), tyrosine (cisplatin-treated kidney), acetylcarnosine (doxorubicin-treated liver), and 2-phosphoglycerate (docetaxel-treated lung) showed similar patterns with S100A8/A9 expression. These metabolites may become useful markers for evaluating S100A8/A9-related tissue damages.