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通过添加尿苷5'-二磷酸葡糖醛酸用微粒体修饰苯并(a)芘代谢。

Modification of benzo(a)pyrene metabolism with microsomes by addition of uridine 5'-diphosphoglucuronic acid.

作者信息

Nemoto N, Takayama S

出版信息

Cancer Res. 1977 Nov;37(11):4125-9.

PMID:908046
Abstract

The metabolism of benzo(a)pyrene (BaP) by rat liver microsomes was examined in the presence and absence of uridine 5'-diphosphoglucuronic acid (UDPGA). BaP metabolites were separated by high-pressure liquid chromatography. The normal chromatographic patterns of the metabolities were altered by the addition of UDPGA. At concentrations of UDPGA at which the elutions of dihydrodiol components were unchanged, phenol and quinone elution profiles were selectively decreased. The decreased activities of microsomal mixed-function oxidases by UDPGA were also observed with the use of the aryl hydrocarbon hydroxylase assay. The decrease may not be due to inhibition of those enzymes, but rather to formation of glucuronide conjugates with oxygenated BaP metabolites. These results suggest that glucuronidation may be important in the detoxification of BaP.

摘要

在存在和不存在尿苷5'-二磷酸葡萄糖醛酸(UDPGA)的情况下,研究了大鼠肝脏微粒体对苯并(a)芘(BaP)的代谢。通过高压液相色谱法分离BaP代谢物。添加UDPGA后,代谢物的正常色谱图发生了改变。在UDPGA浓度下,二氢二醇成分的洗脱未发生变化,但苯酚和醌的洗脱曲线选择性降低。使用芳烃羟化酶测定法也观察到UDPGA使微粒体混合功能氧化酶的活性降低。这种降低可能不是由于那些酶的抑制,而是由于与氧化的BaP代谢物形成了葡萄糖醛酸缀合物。这些结果表明,葡萄糖醛酸化在BaP的解毒过程中可能很重要。

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