Lower G M, Bryan G T
J Toxicol Environ Health. 1976 Jan;1(3):421-32. doi: 10.1080/15287397609529341.
The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.
研究了犬肝芳基乙酰胺脱乙酰酶系统对致癌物4-乙酰氨基联苯、2-乙酰氨基芴和2-乙酰氨基萘进行脱乙酰化的相对能力。将芳基乙酰胺与未强化的犬肝微粒体一起孵育，并通过比色法定量测定生成的芳基胺来估计酶活性（nmol芳基胺/毫克蛋白质/小时）。犬肝酶系统表现出与啮齿动物肝酶系统相似的特征，即酶活性在肝组织中最高，定位于微粒体亚细胞组分，不需要辅因子，并且受热、氟化钠和硫醇试剂抑制。在五次重复测定中，4-乙酰氨基联苯（84.8±12.4）、2-乙酰氨基芴（52.5±5.1）和2-乙酰氨基萘（8.8±3.3）的相对脱乙酰化速率分别约为10、6和1。作为犬膀胱癌致癌物，4-乙酰氨基联苯被认为比2-乙酰氨基芴更具致癌性，而2-乙酰氨基萘没有可检测到的致癌活性，尽管2-氨基萘是公认的犬膀胱癌致癌物。去除乙酰基可能是膀胱癌发生的必要条件；因此，本研究证明了犬肝脱乙酰酶酶特异性与膀胱对这些致癌芳基乙酰胺的易感性之间存在直接关系。
