Grant M H, Duthie S J, Gray A G, Burke M D
Department of Medicine and Therapeutics, University of Aberdeen, Foresterhill, U.K.
Biochem Pharmacol. 1988 Nov 1;37(21):4111-6. doi: 10.1016/0006-2952(88)90103-7.
In cultured human hepatoma cells phenolphthalein glucuronidation was increased 3-fold by 2 mM phenobarbitone (PB) in the culture medium but not by 25 microM benz(a)anthracene (BA), while 1-naphthol glucuronidation was not increased by either PB or BA. Ethoxyresorufin O-deethylation (EROD) was increased 15-fold by BA but not by PB, while the O-dealkylations of pentoxyresorufin (PROD) and benzyloxyresorufin (BROD) were increased by either PB or BA. The BROD activity increased by BA was sensitive to inhibition by alpha-naphthoflavone whereas that induced by PB was not. This suggests induction of different cytochrome P-450 isoenzymes. Control Hep G2 cells had similar glucuronide conjugation and cytochrome reductase activities to freshly isolated human adult hepatocytes, but had lower O-dealkylation and elevated microsomal epoxide hydrolase activities.
在培养的人肝癌细胞中,培养基中2 mM苯巴比妥(PB)可使酚酞葡萄糖醛酸化增加3倍,但25 μM苯并(a)蒽(BA)则无此作用;而PB和BA均未使1-萘酚葡萄糖醛酸化增加。乙氧基异吩唑酮O-脱乙基酶(EROD)活性被BA增加了15倍,但未被PB增加;而戊氧基异吩唑酮(PROD)和苄氧基异吩唑酮(BROD)的O-脱烷基活性则被PB或BA增加。BA增加的BROD活性对α-萘黄酮的抑制敏感,而PB诱导的则不敏感。这表明诱导了不同的细胞色素P-450同工酶。对照的Hep G2细胞具有与新鲜分离的成人肝细胞相似的葡萄糖醛酸结合和细胞色素还原酶活性,但具有较低的O-脱烷基活性和升高的微粒体环氧化物水解酶活性。