D. Potter, Thu-Ba Thi Tran
Sep 1, 1992
Citations
2
Influential Citations
30
Citations
Quality indicators
Journal
Toxicology letters
Abstract
Ethyl acrylate is a monomer used extensively in polymer manufacturing. Although ethyl acrylate is toxic at high concentrations, it is metabolized and detoxified rapidly at low concentrations. In the current studies, in vitro experiments have demonstrated that [14C]ethyl acrylate reacts with both glutathione (GSH) and protein to give either [14C]3-(glutathion-S-yl)ethylpropionate or covalently bound protein adducts, respectively. The second-order rate constant for [14C]ethyl acrylate conjugation with GSH was determined by quantification of [14C]3-(glutathion-S-yl)ethylpropionate using an HPLC system equipped with a flow-through radioactive detector. The rate constant for conjugation was 32.8 M-1 min-1. Additionally, the apparent second-order rate constants were determined for [14C]ethyl acrylate binding to the protein fraction of 14 whole tissue homogenates. Estimation of total protein binding sites was performed by reacting tissue homogenates with high concentrations of [14C]ethyl acrylate, while rates of binding were determined by reacting tissue homogenates with 200 microM [14C]ethyl acrylate at 37 degrees C for various periods of time. Apparent second-order rate constants for ethyl acrylate binding to protein homogenates were similar to that observed for GSH reacting with ethyl acrylate. The role of GSH-transferase in catalyzing 3-(glutathion-S-yl)ethylpropionate formation also was evaluated with whole tissue homogenates. In most tissues, the GSH-transferases poorly catalyzed the conjugation reaction. However, a significant increase in 3-(glutathion-S-yl)ethylpropionate formation was observed with liver homogenate.