Characterization of a Cytotoxic Factor Induced in Murine Serum after the Intravenous Administration of Dehydrogenation Polymers of Phenylpropenoids (a Class of Synthetic Lignins)

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A cytotoxic factor (CF) appeared in murine serum after the intravenous injection of the dehydrogenation polymers (DHPs) of p-coumaric acid (DHP-pCA), caffeic acid (DHP-CA), and ferulic acid (DHP-FA), which are categorized as a class of synthetic lignins. The highest CF activity was observed 15 min after the i.v. injection of DHP-pCA. CF is likely to be cytocidal through an apoptotic mechanism accompanied by nucleosome-sized DNA fragmentation. CF is extractable with aqueous ethanol and highly stable against heat, proteases, and acid/alkali treatments. The ethanol extract showed cytotoxicity toward various cultured cell lines and also ascites carcinoma cells in vivo. The parent molecules DHPs did not show any appreciable cytotoxicity. After the induction of CF activity, the activity quickly diminished and completely disappeared from the blood stream within an hour or so. The cytotoxicity was observed only when the target cells were exposed to CF for longer than 10 h.