Genotoxicity of Acrylamide and Glycidamide: A Review of the Studies by HPRT Gene and TK Gene Mutation Assays

Abstract

Acrylamide (AA), a proven rodent carcinogen, is found in a variety of commonly consumed human foods, which has raised public health concerns. AA is largely oxidized to the chemically reactive epoxide, glycidamide (GA), by cytochrome P450 2E1. The genotoxic effects of AA and GA have been extensively evaluated. However, the results in mammalian gene mutation tests were inconsistent, especially the genotoxic effects at the HPRT gene and TK gene. In this article, the relevant mutations induced by AA and GA on both gene loci in various test systems involving in vivo and in vitro tests are reviewed. It is confirmed that AA acts directly as a clastogen and produces weakly mutagenic effects at the HPRT gene probably by metabolic conversion of AA to GA. On the other hand, GA is a strong mutagen with high reactivity to DNA, inducing predominantly point mutations. The molecular mutation spectra of AA and GA at the HPRT and TK genes are also compared and summarized here, for better clarifying the mechanisms of mutation induced by these two compounds. These data would help to understand the mutagenicity of AA and its contribution to human cancers.