BIOCHEMICAL MARKERS OF NEUROTOXICITY - RESEARCH STRATEGIES AND EPIDEMIOLOGIC APPLICATIONS

A great deal of attention has been given in the past few years to the development and validation of biomarkers for non-cancer endpoints, to be used in human epidemiological studies. In this brief review, selected aspects of biomarker research, as they apply to the field of neurotoxicology, will be discussed. As biomarkers are often divided into indicators of exposure, effect and susceptibility, one example for each of these classes is presented. Measurements of hemoglobin adducts were developed as a way to monitor exposure to acrylamide (a peripheral neurotoxicant) in animals as well as humans, and have been successfully applied in a field study in occupationally exposed workers. Activity of monoamine oxidase B (MAO-B) in platelets was found to be inversely correlated with the levels of exposure to styrene, suggesting that this biochemical measurement may be a useful effect-related biomarker, though additional studies are needed to understand the mechanistic implications of these findings. Serum paraoxonase activity has been shown in animals to modulate the toxicity of organophosphorus insecticides. Studies in humans have lead to the identification of a genetic polymorphism for this enzyme and to define its underlying molecular basis. Epidemiological studies are needed to determine the relevance of this polymorphism in determining susceptibility to organophosphate toxicity.