TY - JOUR
T1 - The changing view of acrylamide neurotoxicity
AU - LoPachin, Richard M.
N1 - Funding Information:
Research presented in this manuscript was supported by a grant (to R.M.L.) from the National Institute of Environmental Health Sciences (RO1 ES03830-18) and from the Procter and Gamble Co., Cincinnati, OH.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
KW - Carcinogenicity
KW - Nerve terminals
KW - Neurotoxicity
KW - Reproductive toxicity
KW - Toxic axonopathy
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U2 - 10.1016/j.neuro.2004.01.004
DO - 10.1016/j.neuro.2004.01.004
M3 - Article
C2 - 15183015
AN - SCOPUS:2942607445
SN - 0161-813X
VL - 25
SP - 617
EP - 630
JO - Neurotoxicology
JF - Neurotoxicology
IS - 4 SPEC. ISS.
ER -