Carcinogenesis Advance Access originally published online on January 18, 2007
Carcinogenesis 2007 28(3):519-528; doi:10.1093/carcin/bgm006
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A review of mechanisms of acrylamide carcinogenicity
Division of Biology, Beckman Research Institute of the City of Hope National Medical Center, 1450 East Duarte Road, Duarte, CA 91010, USA
* To whom correspondence should be addressed. Tel: +1 626 256 4673 ext. 65918; Fax: +1 626 358 7703; Email: ania{at}coh.org
The fact that acrylamide, a proven rodent carcinogen, is present in significant quantities (up to several mg/kg of foodstuff) in a wide range of commonly consumed human foods is alarming. Attempts to determine a possible involvement of dietary acrylamide in human cancers have not been conclusive, however. To resolve the carcinogenicity of acrylamide to humans, the as yet unknown mechanism of action of acrylamide needs to be unraveled. The present review is a synopsis of research on the known and hypothetical modes of action of acrylamide of relevance for carcinogenesis. Both genotoxic and non-genotoxic modes of action of acrylamide are discussed with special emphasis on DNA adduct-targeted mutagenesis. Mechanistic data are presented from various experimental systems including in vitro experiments and in vivo rodent and human studies with special focus on mouse models. Human exposure data, including estimates of daily intake of dietary acrylamide in different populations and the corresponding cancer risk assessments are provided. The significant gaps in knowledge, which currently preclude a more definitive evaluation of human cancer risk due to exposure to dietary acrylamide, are highlighted. Future directions for research on acrylamide and cancer are outlined, and potential challenges are underscored.
Abbreviations: CYP2E1, cytochrome P450 2E1; GSH, glutathione; Hb, hemoglobin; hprt, hypoxanthine-guanine phosphoribosyl transferase; i.p., intra-peritoneal; N7-GA-Gua, 7-(2-carbamoyl-2-hydroxyethyl)-guanine
Received October 19, 2006; revised January 7, 2007; accepted January 9, 2007.
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