Thompson D C, Josephy P D, Chu J W, Eling T E
Laboratory of Molecular Biophysics, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
Mutat Res. 1992 May 16;279(2):83-9. doi: 10.1016/0165-1218(92)90249-y.
In previous studies on the mutagenicity of anisidine isomers, the ortho isomer was considered to be mutagenic towards standard Ames tester strains, while the para isomer gave equivocal results. In the present study we show that both para- and ortho-anisidine isomers are mutagenic in a Salmonella typhimurium tester strain containing elevated levels of N-acetyltransferase (YG1029). p-Anisidine gave a positive mutagenic response using either hamster S9 or ram seminal vesicle microsomes (RSVM) as an activating system, while o-anisidine gave a positive response only with the hamster S9 fraction. The mutagenic response from p-anisidine was greater than with o-anisidine in each case. In tests with p-anisidine and RSVM, the addition of arachidonic acid was not necessary to observe a mutagenic response. Catalase produced a dose-dependent decrease in the mutagenic response with p-anisidine and RSVM; this indicates that endogenous hydrogen peroxide from the bacteria acts as a substrate for the peroxidase activity of RSVM prostaglandin H synthase. These results demonstrate that both anisidine isomers are mutagenic and that N-acetyltransferase enzymes play an important role in their metabolism to mutagenic species.
在先前关于茴香胺异构体致突变性的研究中，邻位异构体被认为对标准艾姆斯试验菌株具有致突变性，而对位异构体的结果则不明确。在本研究中，我们表明，在含有高水平N - 乙酰转移酶的鼠伤寒沙门氏菌试验菌株（YG1029）中，对位和邻位茴香胺异构体均具有致突变性。对茴香胺使用仓鼠S9或公羊精囊微粒体（RSVM）作为活化系统时产生了阳性致突变反应，而邻茴香胺仅与仓鼠S9组分产生阳性反应。在每种情况下，对茴香胺的致突变反应都大于邻茴香胺。在用对茴香胺和RSVM进行的试验中，添加花生四烯酸对于观察致突变反应并非必要。过氧化氢酶使对茴香胺和RSVM的致突变反应呈剂量依赖性降低；这表明细菌内源性过氧化氢作为RSVM前列腺素H合酶过氧化物酶活性的底物。这些结果表明，两种茴香胺异构体均具有致突变性，并且N - 乙酰转移酶在它们代谢为致突变物质的过程中起重要作用。
