Evaluation of cII gene mutation in the brains of Big Blue mice exposed to acrylamide and glycidamide in drinking water.
Evaluation of cII gene mutation in the brains of Big Blue mice exposed to acrylamide and glycidamide in drinking water.
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DOI：
10.2131/jts.41.719
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Manjanatha MG
中科院分区：
文献类型：
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作者：
Li HF;Shelton SD;Townsend TA;Mei N;Manjanatha MG
由于丙烯酰胺(AA)及其活性环氧化物代谢物缩水甘油酰胺(GA)在各种油炸和烘焙淀粉类食品中都含有大量AA，因此饮食暴露于AA及其活性环氧化物代谢物缩水甘油三胺(GA)会对人体产生潜在的健康风险。AA在啮齿类动物中具有致瘤性，大量研究表明AA对小鼠和大鼠的多个器官具有遗传毒性。尽管AA具有神经毒性，但还没有关于AA在小鼠大脑中诱导基因突变的报道。因此，为了研究AA或其代谢物GA是否可以诱发基因突变，我们对预先处理过的雄性和雌性大蓝小鼠进行了CII突变频率(MF)的筛查和突变类型的评分，这些小鼠在饮用水中分别加入0、1.4和7.0 mM AA或GA，最长达4周。高剂量AA和GA诱导的雄性和雌性CIIMFS相似，但只有雄性诱导的CIIMF显著高于相应的雄性对照MF值(p<；0.05)。对雄性CII突变体的分子分析表明，AA和GA各自诱导的G：C→T：A、A：T→T：A和A：T→C：G易位的发生率至少是赋形剂对照组的2.5倍，在比较AA和GA处理时观察到相似的突变谱。这些结果表明，AA和GA在脑内诱发的MFS和突变类型与AA通过代谢对GA发挥遗传毒性相一致。
Potential health risks for humans from dietary exposure to acrylamide (AA) and its reactive epoxide metabolite, glycidamide (GA), exist because substantial amounts of AA are found in a variety of fried and baked starchy foods. AA is tumorigenic in rodents, and a large number of studies indicate that AA is genotoxic in multiple organs of mice and rats. Although AA is neurotoxic, there are no reports on AA-induced gene mutations in the mouse brain. Therefore, to investigate if gene mutation can be induced by AA or its metabolite GA, we screened brains for cII mutant frequency (MF) and scored for mutation types in previously treated male and female Big Blue mice with 0, 1.4 mM, and 7.0 mM AA or GA in drinking water for up to 4 weeks. High doses of AA and GA induced similar cII MFs in males and females but only the induced cII MF in males was significantly higher than the corresponding male control MF (p < 0.05). Molecular analysis of the cII mutants from males showed that AA and GA each induced at least a 2.5-fold increase in the incidence of G:C → T:A, A:T → T:A, and A:T → C:G transversions compared to the vehicle controls, with similar mutational spectra observed when comparing AA with GA treatment. These results suggest that the MFs and types of mutations induced by AA and GA in the brain are consistent with AA exerting its genotoxicity via metabolism to GA.