Radomski J L, Hearn W L, Radomski T, Moreno H, Scott W E
Cancer Res. 1977 Jun;37(6):1757-62.
The glucuronic acid conjugate of N-hydroxy-4-aminobiphenyl (NOH-4-ABP) has been isolated in relatively pure form from the urine of dogs given 4-aminobiphenyl, utilizing molecular size, ion exchange, adsorption, and partition chromatography. This conjugate is an active mutagen in Salmonella typhimurium strains TA1538 and TA98 but not in TA1535 or TA1537. NOH-4-ABP and 4-nitrosobiphenyl are also highly active in TA1538 and TA98 and inactive in TA1535 and TA1537. These observations support the concept that this conjugate is the water-soluble carrier that delivers the active metabolite to the bladder. A substance of identical chromatographic and spectral properties to the conjugate isolated from dog urine has been synthesized in low yield by the direct condensation of NOH-4-ABP with glucuronic acid. This substance yields NOH-4-ABP on dilute acid hydrolysis. Sodium (N-4-biphenylhydroxylamino-beta-D-glucopyranosid) uronate, the N-O-C isomer, was also synthesized. It was found to have differing chromatographic and chemical properties to the natural conjugate. This evidence suggests that the urinary conjugate is the compound in which conjugation has occurred with the nitrogen atom of the hydroxylamine group rather than the oxygen atom.
利用分子大小、离子交换、吸附和分配色谱法，已从给予4-氨基联苯的狗的尿液中以相对纯的形式分离出N-羟基-4-氨基联苯（NOH-4-ABP）的葡糖醛酸共轭物。这种共轭物在鼠伤寒沙门氏菌TA1538和TA98菌株中是一种活性诱变剂，但在TA1535或TA1537中不是。NOH-4-ABP和4-亚硝基联苯在TA1538和TA98中也具有高活性，而在TA1535和TA1537中无活性。这些观察结果支持这样的概念，即这种共轭物是将活性代谢物输送到膀胱的水溶性载体。通过NOH-4-ABP与葡糖醛酸的直接缩合，已低产率合成了一种与从狗尿中分离出的共轭物具有相同色谱和光谱性质的物质。该物质在稀酸水解时产生NOH-4-ABP。还合成了N-O-C异构体，即（N-4-联苯羟氨基-β-D-吡喃葡萄糖苷）尿酸钠。发现它与天然共轭物具有不同的色谱和化学性质。这一证据表明，尿共轭物是其中与羟胺基团的氮原子而非氧原子发生共轭的化合物。
