Corbett M D, Wei C I, Fernando S Y, Doerge D R, Corbett B R
Carcinogenesis. 1983 Dec;4(12):1615-8. doi: 10.1093/carcin/4.12.1615.
The synthesis and purification of N-hydroxy-N-formyl-p-phenetidine (N-OH-FP) is described. This new compound was subjected to mutagenicity testing using Salmonella typhimurium strains TA98, TA100, TA1535, TA1537 and TA1538 both in the presence and absence of the post-mitochondrial fraction of rat liver homogenate. Simultaneous mutagenicity testing of the known phenacetin metabolite, N-hydroxyphenacetin (N-OH-AP), was conducted with the same tester strains. The N-formyl derived hydroxamic acid (N-OH-FP) was found to be a much stronger mutagen than N-hydroxy-phenacetin (N-OH-AP). Furthermore, N-OH-FP also behaved as a direct-acting mutagen unlike N-OH-AP. The chemical stabilities of N-OH-AP and N-OH-FP were studied in phosphate buffer in the pH range of 3-8; and both the hydroxamic acids were found to be stable to the conditions employed. The results of this study support the hypothesis that enzymatic deacylation is an activation process for the expression of mutagenicity by hydroxamic acids.
描述了N-羟基-N-甲酰基-对乙氧基苯胺（N-OH-FP）的合成与纯化。使用鼠伤寒沙门氏菌TA98、TA100、TA1535、TA1537和TA1538菌株，在有和没有大鼠肝脏匀浆线粒体后成分存在的情况下，对这种新化合物进行了致突变性测试。同时，用相同的测试菌株对已知的非那西丁代谢物N-羟基非那西丁（N-OH-AP）进行了致突变性测试。发现N-甲酰基衍生的异羟肟酸（N-OH-FP）比N-羟基非那西丁（N-OH-AP）是更强的致突变剂。此外，与N-OH-AP不同，N-OH-FP也表现为直接作用的致突变剂。在pH值为3 - 8的磷酸盐缓冲液中研究了N-OH-AP和N-OH-FP的化学稳定性；发现两种异羟肟酸在所采用的条件下都是稳定的。本研究结果支持这样的假设，即酶促脱酰作用是异羟肟酸表达致突变性的激活过程。
