Baum Matthias, Loeppky Richard N, Thielen Silke, Eisenbrand Gerhard
Department of Chemistry, Division of Food Chemistry and Toxicology, University of Kaiserslautern, Erwin-Schroedinger-Strasse 52, Kaiserslautern 67663, Germany.
J Agric Food Chem. 2008 Aug 13;56(15):5989-93. doi: 10.1021/jf703741a. Epub 2008 Jul 15.
Acrylamide (AA) is generated by thermal processing of foods, depending on processing conditions and precursor availability. AA is not genotoxic by itself but becomes activated to its genotoxic metabolite glycidamide (GA) via epoxidation, mediated primarily by cytochrome P450 2E1. In the Comet assay in V79 cells and in human lymphocytes, GA induced DNA damage down to 300 microM concentration (4 h). After post-treatment with the DNA repair enzyme formamidopyrimidine-DNA-glycosylase (FPG), DNA damage became already detectable at 10 microM (4 h). By comparison, the N-nitroso compound 3- N-nitroso-oxazolidin-2-one (NOZ-2) is a much stronger genotoxic agent, significantly inducing DNA damage already at 15 min (3 microM). Post-treatment with FPG in this case did not enhance response. GA induced DNA damage in V79 cells rather slowly, with first response detectable at 4 h. The hPRT forward mutation test encompasses 5 days of expression time during which also repair can take place. GA-induced hPRT mutations only became detectable at concentrations of 800 microM and above. This is 80-fold higher than the lowest significant response to GA in the Comet assay (10 microM with FPG). In contrast, NOZ-2 was as effective in the hPRT test as in the Comet assay (3 microM). These results demonstrate substantial differences in the genotoxic potency of GA and NOZ-2. Whereas NOZ-2 is a pontent genotoxic mutagen, GA in comparison shows only low genotoxic and mutagenic potential, presumably as a result, at least in part, of preferential N7-G alkylation.
丙烯酰胺（AA）是食品热加工过程中产生的，具体取决于加工条件和前体物质的可获得性。AA本身没有基因毒性，但通过环氧化作用被激活成为其具有基因毒性的代谢产物环氧丙酰胺（GA），这一过程主要由细胞色素P450 2E1介导。在V79细胞和人淋巴细胞的彗星试验中，GA在浓度低至300微摩尔（4小时）时就能诱导DNA损伤。在用DNA修复酶甲酰胺嘧啶-DNA-糖基化酶（FPG）进行后处理后，在10微摩尔（4小时）时就能检测到DNA损伤。相比之下，N-亚硝基化合物3-亚硝基-恶唑烷-2-酮（NOZ-2）是一种更强的基因毒性剂，在15分钟（3微摩尔）时就能显著诱导DNA损伤。在这种情况下，用FPG进行后处理并没有增强反应。GA在V79细胞中诱导DNA损伤的速度相当缓慢，4小时时才能检测到最初的反应。hPRT正向突变试验包括5天的表达时间，在此期间也会发生修复。GA诱导的hPRT突变只有在浓度达到800微摩尔及以上时才能检测到。这比彗星试验中对GA的最低显著反应（FPG处理时为10微摩尔）高80倍。相比之下，NOZ-2在hPRT试验中的效果与彗星试验中一样（3微摩尔）。这些结果表明GA和NOZ-2在基因毒性效力上存在显著差异。虽然NOZ-2是一种强大的基因毒性诱变剂，但相比之下，GA仅显示出较低的基因毒性和诱变潜力，这可能至少部分是由于优先发生N7-G烷基化的结果。
