Toxicity of sulfur mustard in primary neuron culture.
The toxicity of sulfur mustard (HD) was assessed in primary cultures of chick embryo forebrain neurons using several different endpoints. Mature neurons were found to be very sensitive to the toxic effects of this agent and tritiated arachidonic acid release, as well as the MTT, neutral red and alamarBlue cytotoxicity assays all gave LC(50) values in the low mum range. Maximal toxicity was initiated within minutes of culture exposure to HD and was not found to be associated with toxic mediator release into the medium. The characteristics of toxicity were quite different when comparing immature cultures to mature ones. Mature cultures were more sensitive to the toxicity of HD than were immature cultures, and maximal toxicity in mature cultures took longer to be expressed. In addition, the toxicity was found to be dependent on the initial seeding density, as well as on the age of the cultures at the time of chemical treatment. Although the reasons for these observations are unclear, the apparent dependence of HD toxicity on the differentiative maturity of the cultures may eventually provide some clues as to the mechanism of action of this chemical agent. Furthermore, the extreme sensitivity 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.
Sawyer
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Medical Countermeasures Section, Defence Research Establishment Suffield, Box 4000, Medicine Hat, Alberta, Canada T1A 8K6.