| 1 . ObjectivesAcrylamide (AA) is a highly water-soluble, small molecule, a,b-unsaturated carbonyl compound which may be absorbed through the skin quickly. Industrially, AA is used primarily for the production of polyacrylamides. These polymers have their largest market as flocculants for the purification of water, waste water treatment, food processing, paper and mineral processing, while the monomer is used to produce grouts and soil stabilizer in the construction of dams, foundations, tunnels and roadways. It also has some minor uses in the manufacture of adhesives, the textile industry, and some photographic applications. The number of workers exposed to AA in industrial processes may be several thousand worldwide and the population potentially exposed to AA in molecular biological laboratories is estimated to be as high as 100,000-200,000. Recent studies reported that AA is formed in the heating of starch and meat food, suggesting that human exposure to AA could occur during cooking and through ordinary diet. In contrast to itsnontoxic polymeric forms, AA can cause several toxic effects and has the potential mutagenesis and carcinogenesis risk to human. Thus, to demonstrate the genotoxicity and carcinogenicity of AA to human and to clarify its mechanism of action are now in urgent needs.AA is known to produce a wide range of toxic effects, including neurotoxicity, genotoxicity, reproductive toxicity and carcinogenicity. More recently, increasing attention has been given to its genotoxic and cancer inductive properties. AA has been shown to induce structural chromosomal aberrations and mitotic disturbances, but often failed in inducing transformation and gene mutation in mammalian cells in vitro. AA induced chromosomal aberrations and micronuclei formation in mouse bone marrow and in premeiotic and postmeiotic cells. Treatment with acrylamide in vivo also caused somatic mutation, heritable translocation and specific locus mutations in mice and dominant lethal mutations in both mice and rats in several studies. Acrylamide induces unscheduled DNA synthesis in rat spermatocytes, mice germ cells and human mammary epithelial cells, but apparently not in rat hepatocytes. Acrylamide also induces sex-linked recessive lethal and somatic mutations in Drosophila. It does not induce mutation even in very high dose in bacteria such as Salmonella, klebsiella pneumoniae and Escherichia coli. Besides, AA was first shown to be carcinogenic in 1984 by Bull when given to mice orally, topically or by intraperitoneal injection, and later its carcinogenicity was demonstrated in rats when administered through the drinking water. Based on the combined evidence from these animal studies, AA has been classified by the IARC as "probably carcinogenic to humans", since epidemiological investigations of exposed workers have not shown an association between AA exposure and cancer in humans.Most researchers have found that AA induces transmissible genetic effectssuch as chromosome aberrations and sister chromatid exchanges, but in the observation of DNA damage and gene mutation, both positive and negative results were reported. A phenomenon which has so far eluded a satisfactory explanation is that although some studies have shown that AA binds to DNA directly via Michael addition reaction in vitro and in vivo, it consistently gives a negative response in the Ames test, both with or without microsomal activation. Until recently, only a few studies have been performed with the purpose of studying the mechanism of AA toxic action. It has been reported that AA reacts extremely weakly with DNA in vitro, producing significant levels of adducts only after several weeks with very high concentration of AA. So it has been proposed that the genotoxic and carcinogenic effects of AA are a consequence of its interaction with proteins. AA appears to be metabolized into glycidamide (GA) via cytochrome P450 (CYP450) 2E1. Recently, it was shown that the epoxide GA, which can be formed from AA by CYP450 mediated metabolism, s...
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