High Technology Mass Spectrometry Laboratory
Abstract
Preparedness for acts of chemical terrorism and warfare require detection and response. Chemical testing will allow for diagnosis of exposed individuals. Acrylonitrile (AN) is a toxic industrial chemical produced in large quantities by the chemical industry and is acutely toxic. Our objective was to define the chemical signatures of AN-adducts in human blood following an exposure. In this project we have measured the second order rate constants for the reaction of AN with the most reactive sites in human blood in vitro. Human blood, red blood cell lysates and plasma were incubated, under pseudo first-order conditions, with 100mM AN at 37 deg C and the disappearance of glutathione (GSH) and the appearance of the AN-adducts of GSH, hemoglobin beta-Cys93 (Hb.C93-AN) and albumin Cys34 (AbC34-AN) were monitored. The second order rate constants in M-1s-1 were: disappearance of GSH in whole blood, 0.0806; appearance of GS-AN in whole blood, 0.0776, appearance of Hb.C93-AN in rbc lysate, 0.000722 and appearance of AbC34-AN in plasma, 0.224. The data indicate that the most reactive site for AN in human blood is Cys34 of albumin. This site reacts 2.8 times faster than GSH and 310 times faster than Hb.C93 and thus will serve as an excellent biomarker of AN exposure.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2010
- Accession Number
- ADA530590
Entities
People
- Frederick W. Benz
Organizations
- University of Louisville