Toxicity of sulfur mustard in primary neuron culture

The toxicity of sulfur mustard (HD) was assessed in primary cultures of chi ck embryo forebrain neurons using several different endpoints. Mature neuro ns were found to be very sensitive to the toxic effects of this agent and t ritiated arachidonic acid release, as well as the MTT, neutral red and alam arBlue cytotoxicity assays all gave LC50 values in the low mu M range. Maxi mal toxicity was initiated within minutes of culture exposure to HD and was not found to be associated with toxic mediator release into the medium. Th e characteristics of toxicity were quite different when comparing immature cultures to mature ones. Mature cultures were more sensitive to the toxicit y of HD than were immature cultures, and maximal toxicity in mature culture s took longer to be expressed. In addition, the toxicity was found to be de pendent on the initial seeding density, as well as on the age of the cultur es at the time of chemical treatment. Although the reasons for these observ ations are unclear, the apparent dependence of HD toxicity on the different iative maturity of the cultures may eventually provide some clues as to the mechanism of action of this chemical agent. Furthermore, the extreme sensi tivity of these cells to the toxic effects of HD makes them a useful model system with which to screen for potential protective drug regimens against this chemical warfare agent. Crown copyright (C) 1999 Published by Elsevier Science Ltd. All rights reserved.