Chou M W, Pegram R A, Turturro A, Holson R, Hart R W
National Center for Toxicological Research, Jefferson, Arkansas 72079.
Drug Chem Toxicol. 1993;16(1):1-19. doi: 10.3109/01480549309038659.
While it is known that caloric restriction alters activities of certain xenobiotic metabolizing enzymes, the mechanism(s) by which this occurs have not been determined. In this study, caloric restriction (CR) increases activities of liver cytochrome P450IA1 dependent ethoxyresorufin-O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) and cytochrome P450IIB1 dependent pentoxyresorufin-O- dealkylase (PROD) in DBA/2J or C57BL/6N mice. However, the cytosolic Ah receptor binding in both strains of mice was not increased. The hepatic cytochrome P450IA1 activity was increased by CR in DBA/2J mice (a strain lacking normal Ah receptor binding), indicating that this induction need not be mediated by the Ah receptor. The effects of CR, sex and strain on P450IA1 induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were also determined. Specific induction of cytochrome P450IA1 by TCDD was greater in females than in males of both strains, whereas the P450 isozymes induced in male DBA/2J mice had less specificity toward 7-ethoxyresorufin than those induced in C57BL/6N mice. Moreover, P450IA1 induction by TCDD was significantly potentiated by CR in the DBA/2 strain, indicating the interactive involvement of different regulatory mechanisms.
虽然已知热量限制会改变某些外源性物质代谢酶的活性，但这种现象发生的机制尚未确定。在本研究中，热量限制（CR）可增加DBA/2J或C57BL/6N小鼠肝脏中细胞色素P450IA1依赖性乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）和芳烃羟化酶（AHH）以及细胞色素P450IIB1依赖性戊氧基异吩恶唑酮 - O - 脱烷基酶（PROD）的活性。然而，两种品系小鼠的胞质Ah受体结合并未增加。在DBA/2J小鼠（一种缺乏正常Ah受体结合的品系）中，CR可增加肝脏细胞色素P450IA1的活性，这表明这种诱导不一定由Ah受体介导。还确定了CR、性别和品系对2,3,7,8 - 四氯二苯并 - p - 二恶英（TCDD）诱导P450IA1的影响。在两个品系中，TCDD对细胞色素P450IA1的特异性诱导在雌性中均高于雄性，而雄性DBA/2J小鼠中诱导的P450同工酶对7 - 乙氧基异吩恶唑酮的特异性低于C57BL/6N小鼠中诱导的同工酶。此外，在DBA/2品系中，CR可显著增强TCDD对P450IA1的诱导作用，这表明不同调节机制之间存在相互作用。
