The enzymatic reduction of the N-hydroxy derivatives of 2-acetylaminofluorene and related carcinogens by tissue preparations.
The enzymatic reduction of the N-hydroxy derivatives of 2-acetylaminofluorene and related carcinogens by tissue preparations.
复制标题
通过组织制剂酶促还原 2-乙酰氨基芴的 N-羟基衍生物和相关致癌物。
作者：
P. Lotlikar;E. Miller;J. Miller;A. Margreth
总结开发了将N-羟基-2-乙酰基-氨基芴和相关异羟肟酸（7-氟-2-乙酰基氨基芴、4-乙酰基氨基芪、2-乙酰基氨基菲和2-乙酰基氨基萘的N-羟基衍生物）还原为其各自酰胺的酶系统的测定法。一些胺也形成作为脱乙酰化的结果。为了获得最大活性，将用吡啶核苷酸强化的未分级匀浆在pH 7.8下在氮气氛中孵育。证明不需要黄素核苷酸。2-硝基芴没有减少肝匀浆是否与黄素核苷酸强化的介质。肝脏是研究的N-羟基-2-乙酰氨基芴还原最活跃的组织。大鼠肾脏、小肠粘膜、肾上腺或睾丸的活性为大鼠肝脏的10-20%。各种肝肿瘤的活性高达成年大鼠肝脏的40%。在N-羟基-2-乙酰氨基芴的还原中，小鼠和家兔肝脏的活性是大鼠肝脏的数倍;小鼠和豚鼠肝脏的活性较低。豚鼠和仓鼠肝匀浆也引起广泛的脱乙酰化。在试验条件下，肝匀浆可将N-羟基-2-氨基芴和2-亚硝基芴轻易还原为2-氨基芴;酶促还原的定量要求在分析过程中排除空气、酸和碱。2-亚硝基芴而不是N-羟基-2-氨基芴与还原型谷胱甘肽在空气或氮气气氛中在pH 7.8下反应，得到水溶性产物。2-将本品与肝匀浆孵育或在氮气下用酸或碱处理，可获得氨基芴。介绍了新化合物2-亚硝基芴的合成方法。
Summary An assay was developed for the enzyme system that reduces N-hydroxy-2-acetyl-aminofluorene and related hydroxamic acids (the N-hydroxy derivatives of 7-fluoro-2-acetylaminofluorene, 4-acetylaminostilbene, 2-acetylaminophenanthrene, and 2-acetylaminonaphthalene) to their respective amides. Some amine was also formed as a consequence of deacetylation. For maximum activity unfractionated homogenates fortified with pyridine nucleotides were incubated at pH 7.8 in a nitrogen atmosphere. No requirement for flavin nucleotides was demonstrated. 2-Nitrofluorene was not reduced by liver homogenates whether or not the medium was fortified with flavin nucleotides. Liver was the most active of the tissues studied for the reduction of N-hydroxy-2-acetylaminofluorene. Rat kidney, small intestinal mucosa, adrenals, or testes had 10–20% of the activity of rat liver. Various liver tumors had activities up to 40% that of adult rat liver. Hamster and rabbit liver were several times as active in the reduction of N-hydroxy-2-acetylaminofluorene as rat liver; mouse and guinea pig liver were less active. Guinea pig and hamster liver homogenates also caused extensive deacetylation. N-Hydroxy-2-aminofluorene and 2-nitrosofluorene were readily reduced to 2-aminofluorene by liver homogenates under the assay conditions; quantitation of the enzymatic reduction required the exclusion of air, acid, and alkali during the analytical prcedures. 2-Nitrosofluorene, but not N-hydroxy-2-aminofluorene, reacted with reduced glutathione at pH 7.8 in an air or nitrogen atmosphere to yield a water soluble product. 2-Aminofluorene was obtained on incubation of this product with liver homogenate or by treatment with acid or alkali under nitrogen. The synthesis of 2-nitrosofluorene, a new compound, is described.