The Changing View of Acrylamide Neurotoxicity

Acrylamide (ACR) is a water-soluble, vinyl monomer that has multiple chemical and industrial applications: e.g., waste water management, ore processing. In addition, ACR is used extensively in molecular laboratories for gel chromatography and is present in certain foods that have been prepared at very high temperatures. Extensive studies in rodents and other laboratory animals have provided evidence that exposure to monomeric ACR causes cellular damage in both the nervous and reproductive systems, and produces tumors in certain hormonally responsive tissues. Whereas human epidemiological studies have demonstrated a significantly elevated incidence of neurotoxicity in occupationally exposed populations, such research has not, to date, revealed a corresponding increase in cancer risk. Since the announcement by a Swedish research group in April 2002 [J. Ag. Food Chem. 50 (2002) 4998] regarding the presence of ACR in potato and grain-based foods, there has been a renewed interest in the toxic actions of this chemical. Therefore, in this review, we consider the different toxic effects of ACR. The neurotoxic actions of ACR will be the focal point since neurotoxicity is a consequence of both human and laboratory animal exposure and since this area of investigation has received considerable attention over the past 30 years. As will be discussed, a growing body of evidence now indicates that the nerve terminal is a primary site of ACR action and that inhibition of corresponding membrane-fusion processes impairs neurotransmitter release and promotes eventual degeneration. The electrophilic nature of ACR suggests that this neurotoxicant adducts nucleophilic sulfhydryl groups on certain proteins that are critically involved in membrane fusion. Adduction of thiol groups also might be common to the reproductive and carcinogenic effects of ACR. A final goal of this review is to identify data gaps that retard a comprehensive understanding of ACR pathophysiological processes.