In Vitro Adduct Formation of Phosgene with Albumin and Hemoglobin in Human Blood

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• 作者：Daan Noort ; Albert G. Hulst ; Alex Fidder ; Ronald A. van Gurp ; Leo P. A. de Jong ; and Hendrik P. Benschop
• 刊名：Chemical Research in Toxicology
• 出版年：2000
• 出版时间：August 2000
• 年：2000
• 卷：13
• 期：8
• 页码：719 - 726
• 全文大小：171K
• 年卷期：v.13,no.8(August 2000)
• ISSN：1520-5010

文摘

The development of procedures for retrospective detection and quantitation of exposure tophosgene, based on adducts to hemoglobin and albumin, is described. Upon incubation of humanblood with [¹⁴C]phosgene (0-750 ages/entities/mgr.gif">M), a significant part of radioactivity (0-13%) becameassociated with globin and albumin. Upon Pronase digestion of globin, one of the adducts wasidentified as the pentapeptide O=C-(V-L)-S-P-A, representing amino acid residues 1-5 ofages/gifchars/alpha.gif" BORDER=0>-globin, with a hydantoin function between N-terminal valine and leucine. Micro-LC/tandemMS analyses of tryptic as well as V8 protease digests identified one of the adducts to albuminas a urea resulting from intramolecular bridging of lysine residues 195 and 199. The adductedtryptic fragment could be sensitively analyzed by means of micro-LC/tandem MS with multiple-reaction monitoring (MRM), enabling the detection in human blood of an in vitro exposurelevel of ages/entities/ge.gif">1 ages/entities/mgr.gif">M phosgene.