Acrylamide Binding to Its Cellular Targets: Insights from Computational Studies

Abstract

Acrylamide (AC, CH2=CH–CONH2, Chart 1), present in heated foodstuffs [Rice, 2005], has been classified by the International Agency for Research on Cancer as ‘‘probably carcinogenic to humans” (group 2A) (IARC, 1994). The Scientific Committee on Toxicity, Ecotoxicity and the Environment (CSTEE) in the European Union (EU) demonstrated that AC exposure to humans should be controlled as low as possible because of its inherently toxic properties [Zhang et. al., 2009; Dearfield et. al., 1995]. AC is a low molecular-weight, odorless, and colorless compound. It is readily soluble in water and can rapidly polymerize from a monomer state to a polymer form [Klaunig, 2008]. AC is biotransformed in vivo to its epoxide glycidamide (GDE) by cytochrome P450 2E1 (CYP2E1) [Ghanayem et. al., 2005]. GDE has genotoxic properties in both in vitro and in vivo test systems [Kurebayashi & Ohno, 2008]. In spite of the possible carcinogenic nature of AC, no consistent effect of AC exposure on cancer incidence in humans could be identified [Rice, 2005]. This strikingly contrasts with AC subministration in both mice and rats, which may cause tumors at multiple sites [Besaratinia & Pfeifer, 2005; 2007]. A plausible hypothesis is this might be caused, at least partially, by the fact that AC interacts differently with the mouse and human proteins. AC may interact with cysteine residues not engaged in S-S bridges. Indeed, the double bond of conjugated vinyl compounds has strong affinity with SH groups [Friedman, 2003; Carere, 2006].