Genotoxicity of ethyl carbamate (urethane) in Salmonella, yeast and human lymphoblastoid cells
Genotoxicity of ethyl carbamate (urethane) in Salmonella, yeast and human lymphoblastoid cells
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DOI：
10.1016/s0165-1218(96)00160-7
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发表时间：
1997-04-24
影响因子：
1.9
通讯作者：
Luthy, J
中科院分区：
文献类型：
--
作者：
Hubner, P;Groux, PM;Luthy, J
氨基甲酸乙酯是一种已知的致癌物质，存在于发酵食品和饮料中，因此对食品安全保障具有重要意义。我们研究了氨基甲酸乙酯对鼠伤寒沙门氏菌、酿酒酵母和人淋巴母细胞系TK6细胞的遗传毒性。在没有细胞色素P450酶的情况下，在非细胞毒性范围内的三个测试系统中的任何一个中都没有观察到氨基甲酸乙酯介导的遗传毒性。在激活体系存在下，氨基甲酸乙酯对鼠伤寒沙门氏菌TA100菌株有致突变作用，而对TA98和TA102菌株则无致突变作用，表明G-C碱基对发生了碱基置换。相比之下，氨基甲酸乙酯在人淋巴母细胞系TK6细胞中未检测到明显的致突变作用。然而，在细胞毒性浓度下，氨基甲酸乙酯在没有P45O介导的代谢激活的情况下对酿酒酵母具有遗传毒性。P450IIE1的抑制剂(DMSO、乙醇和二硫代二乙基氨基甲酸酯)以剂量依赖的方式减弱氨基甲酸乙酯对鼠伤寒沙门氏菌TA100的致突变作用，提示P4SOIIEI是激活酶。
Ethyl carbamate is a known carcinogen occurring in fermented food and beverages and is therefore of interest for food safety assurance. We studied the genotoxicity of ethyl carbamate in Salmonella typhimurium, in Saccharomyces cerevisiae and in human lymphoblastoid TK6 cells. In absence of cytochrome P450 enzymes, no ethyl carbamate-mediated genotoxicity was observed in any of the three test systems in the non-cytotoxic range. In the presence of an activating system, ethyl carbamate was found to be mutagenic in Salmonella typhimurium strain TA100 but not in strains TA98 and TA102, indicating base-pair substitutions at G-C base pairs. In contrast, no significant mutagenicity of ethyl carbamate could be detected in human lymphoblastoid TK6 cells. However, applied in cytotoxic concentrations, ethyl carbamate was genotoxic for Saccharomyces cerevisiae in the absence of P45O-mediated metabolic activation. Inhibitors of P450IIE1 (DMSO, ethanol and dithiodiethylcarbamate) diminished ethyl carbamate-mediated mutagenicity in Salmonella typhimurium strain TA100 in a dose dependent manner, suggesting that P4SOIIEI is the activating enzyme.