Mikhailova Olga N, Gulyaeva Lyudmila F, Filipenko Maxim L, Kaledin Vasily I
Institute of Molecular Biology and Biophysics, Novosibirsk 630117, Russia.
Mutat Res. 2007 Aug 15;632(1-2):99-103. doi: 10.1016/j.mrgentox.2007.04.013. Epub 2007 Apr 29.
CYP1A2 expression is constitutively high in mouse liver and is well known for metabolizing several drugs and many procarcinogens to reactive intermediates that can cause toxicity or cancer. In the present study, the basal level of hepatic CYP1A2 activity was shown to vary among different inbred mouse strains. The highest methoxyresorufin-O-demethylase activity (261+/-52pmol/mgprotein/min) was registered in CC57BR and the lowest (82+/-11pmol/mgprotein/min) in C3H/a. We have tested the hypothesis that possible polymorphisms in regulatory elements in the 5'-upstream region of the mouse CYP1A2 gene could cause the differences in CYP1A2 enzyme activity among different inbred strains. We have performed a study on the CYP1A2 gene by sequencing the regulatory region from -4675 to -4204 where two enhancer elements were recently identified. The absence of mutation prescribing the phenotype in the CYP1A2 gene was found. The region studied seems to be a highly conserved in mice and not to be associated with interstrain differences in constitutive CYP1A2 enzyme activity.
CYP1A2在小鼠肝脏中的表达呈组成性高表达，并且以将多种药物和许多前致癌物代谢为可导致毒性或癌症的反应性中间体而闻名。在本研究中，肝脏CYP1A2活性的基础水平在不同的近交小鼠品系中显示出差异。最高的甲氧基试卤灵-O-脱甲基酶活性（261±52pmol/mg蛋白质/分钟）在CC57BR中测得，最低的（82±11pmol/mg蛋白质/分钟）在C3H/a中测得。我们检验了这样一个假设，即小鼠CYP1A2基因5'-上游区域调控元件中可能存在的多态性可能导致不同近交品系间CYP1A2酶活性的差异。我们通过对从-4675到-4204的调控区域进行测序，对CYP1A2基因进行了研究，在该区域最近发现了两个增强子元件。在CYP1A2基因中未发现规定该表型的突变。所研究的区域在小鼠中似乎高度保守，并且与组成型CYP1A2酶活性的品系间差异无关。
