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Title:   Author  item
                                            WILLIAMS, JOHN - Jacksonville State Universityitem
                                            RAYBURN, JAMES - Jacksonville State Universityitem
                                            CLINE, GEORGE - Jacksonville State Universityitem
                                            SAUTERER, ROGER - Jackson State Universityitem
                                            Friedman, Mendel
  Submitted to: Journal of Agricultural and Food Chemistry
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 7/14/2014
                                    Publication  Date: 7/23/2014
                                    Citation: Williams, J.R., Rayburn, J.R., Cline, G.R., Sauterer, R., Friedman, M. 2014. Potential protective effect of L-cysteine against the toxicity of acrylamide and furan in exposed Xenopus laevis embryos: an interaction study. Journal of Agricultural and Food Chemistry. 62(31):7927-7938. DOI: 10.1021/jf5013743.Interpretive Summary: Reports that potential toxic acrylamide and furan are present in foods (bread, coffee, potato fries) formed during their processing (baking, frying, grilling) heightened interest in the chemistry, biochemistry, and safety of these reactive molecules.  In vivo, acrylamide is reported to act as a carcinogen, neurotoxin, and reproductive toxin, whereas furan is reported to induce hepatocarcinogenicity in rodents, so it is considered to be a presumptive carcinogen. In a collaborative study with the Biology Department of Jackson State University, Alabama, we explored the protective effect of the amino acid L-cysteine against malformation in frog embryos induced by these two toxins. The amino acid L-cysteine, commercially used as a dough additive to increase bread volume  seems to protect the embryos against teratogencity at very low concentrations of L-cysteine to acrylamide, in particular the reduction of severe acrylamide malformations (i.e. edema, facial and gut coiling). Our results indicate that L-cysteine has the potential to overcome adverse effects in individuals consuming the amounts of acrylamide present in processed food.
                                Technical Abstract: The embryo toxicities of two food-processing-induced toxic compounds, acrylamide and furan, with and without added L-cysteine were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus (FETAX).  The following measures of developmental toxicity were used (a) 96-h LC50, the median concentration causing 50% embryo lethality; (b) 96-h EC50, the median concentration causing 50% malformations of the surviving embryos; and (c) teratogenic index (96-h LC50/96-h EC50), an estimate of teratogenic risk.  Calculations of toxic units (TU) were used to assess possible antagonism, synergism or response addition of several mixtures.  The evaluated compounds demonstrated counter-intuitive effects.  Furan had lower than expected toxicity in Xenopus embryos and unlike acrylamide, does not seem to be teratogenic.  However, the short duration of the tests may not show the full effects of furan if it is truly primarily genotoxic and carcinogenic.  L-cysteine showed unexpected properties in the delay of hatching of the embryos.  The results from the interaction studies between combination of two or three components (acrylamide plus L-cysteine; furan plus L-cysteine; acrylamide plus furan; acrylamide plus furan and L-cysteine) show that furan and acrylamide seem to have less than response addition at 1:1 toxic unit ratio in lethality.  Acrylamide and L-cysteine show severe antagonism even at low ratios of 19 acrylamide : 1 L-cysteine TU ratios.  Data from the mixture of acrylamide, furan, and L-cysteine show a slight antagonism, less than would have been expected from binary mixture exposures.  Bioalkylation mechanisms and their prevention are discussed.  There is a need to study the toxicological properties of mixtures of acrylamide and furan concurrently formed in heat-processed food.


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