title: Detoxification of selenite to form selenocyanate in mammalian cells.
abstract: When human hepatoma HepG2 cells were exposed to sodium selenite, an unknown selenium metabolite was detected in the cytosolic fraction by HPLC-inductively coupled plasma mass spectrometry (ICP-MS). The unknown selenium metabolite was also detected in the mixture of HepG2 homogenate and sodium selenite in the presence of exogenous glutathione (GSH). The unknown selenium metabolite was identified as selenocyanate by electrospray ionization mass spectrometry (ESI-MS) and ESI quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS). Because exogenous cyanide increased the amount of selenocyanate in the mixture, selenocyanate seemed to be formed by the reaction between selenide or its equivalent, the product of the reduction of selenite, and endogenous cyanide. Rhodanase, an enzyme involved in thiocyanate synthesis, was not required for the formation of selenocyanate. Selenocyanate was less toxic to HepG2 cells than selenite or cyanide, suggesting that it was formed to reduce the toxicity of selenite. However, selenocyanate could be assimilated into selenoproteins and selenometabolites in rats in the same manner as selenite. Consequently, selenite was metabolized to selenocyanate to temporarily ameliorate its toxicity, and selenocyanate acted as an intrinsic selenium pool in cultured cells exposed to surplus selenite.
authors.affiliation: Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University , Machida, Tokyo 194-8543, Japan.
authors.forename: Yasumi
authors.initials: Y
authors.lastname: Anan
authors.affiliation: Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University , Machida, Tokyo 194-8543, Japan.
authors.forename: Momoko
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University , Machida, Tokyo 194-8543, Japan.
authors.forename: Marina
authors.initials: M
authors.lastname: Hayashi
authors.affiliation: Laboratory of Chemical Toxicology and Environmental Health, Showa Pharmaceutical University , Machida, Tokyo 194-8543, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Koike
authors.affiliation: Department of Toxicology and Environmental Health, Graduate School of Pharmaceutical Sciences, Chiba University , Chuo, Chiba 260-8675, Japan.
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Ogra
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003485:Cyanates / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D017208:Rats, Wistar; D020887:Selenious Acid / Q000378:metabolism*; D018036:Selenium Compounds / Q000378:metabolism*
chemical_list: D003485:Cyanates; D018036:Selenium Compounds; C053721:selenocyanic acid; D020887:Selenious Acid