The goal of this proposal is to continue studying the mechanism(s) and develop specific markers of the neurotoxic action resulting from exposure to neurotoxic chemicals, a situation that is frequently encountered in industry (1). We will continue studying the mechanism of the joint neurotoxic action of EPN and aliphatic hexacarbons at the neurotoxicity target, the brain and spinal cord. We will also carry out studies to develop a clinical marker, by producing monoclonal antibodies to these specific neurotoxicants, for detecting and testing for exposure of workers to these chemicals. We will divide the proposal into four major sections, although there will be significant overlap in the studies in each of these sections. 1. Development of specific monoclonal antibodies to neurotoxic chemicals. 2. Study the mechanism of action of CS2 and hexacarbon induced neurotoxicities. 3. Study the relationship of the immune system to the development of neurotoxicity. 4. Continue work on the mechanism of interaction of aliphatic hexacarbons and EPN on the brain and spinal cord. In the first section we will investigate the development of monoclonal antibodies to specific neurotoxic chemicals. These antibodies would be chemical specific and would recognize protein bound neurotoxicant, independent of which protein the compound in bound. These antibodies would therefore be useful in the clinical diagnosis of exposure to these compounds. The second section will focus on the mechanism of action of these compounds on the nervous system. Since CS2 and hexacarbons produce nearly identical pathologies we will investigate if there is a common mechanism of action of these two classes of compounds. In the third section, we will investigate the possible role of the immune system on nerve degeneration that is observed after exposure to the chemicals which can covalently modify proteins, thus creating a hapten or foreign substance which is then recognized by the immune system. In the final section we continue work on the joint mechanism of action of organophosphorus compounds and hexacarbon compounds. In this work will focus on the role of cytochrome P-450 in the nervous system on the joint mechanism of action of these compounds.
