Iba M M, Fung J, Thomas P E, Park Y
Department of Pharmacology and Toxicology, Rutgers University, EOHSI, Piscataway, NJ 08854, USA.
Arch Toxicol. 1999 Jun-Jul;73(4-5):208-16. doi: 10.1007/s002040050608.
Adult male and female Sprague-Dawley rats were compared in terms of the constitutive levels and inducibility of CYP1A1 and CYP1A2 (CYP1A) in lung, kidney, and liver. CYP1A were induced by i.p. treatment with pyridine (75 mg/kg per day) or beta-naphthoflavone (betaNF; 25 mg/kg per day) for two consecutive days and analyzed catalytically (via O-dealkylation of resorufin ethers), at the protein level (by Western blot analysis) and at the mRNA level (by Northern blot analysis). In untreated rats. CYP1A1 protein and its mRNA were detectable only in the lung and kidney of females but not males, whereas CYP1A2 protein and its mRNA were detectable only in the liver in either gender. Pyridine treatment upregulated CYP1A1 mRNA and its protein in the lung, kidney and liver in female rats, and upregulated the mRNA but not the protein in the lung and liver in male rats. Conversely, pyridine induced both CYP1A2 mRNA and protein in the liver in female rats, whereas it induced the protein but not its mRNA in the liver in male rats. No gender difference was observed in the plasma elimination rate of administered pyridine. BetaNF, in contrast to pyridine, induced CYP1A proteins, activities, and mRNA to higher levels in male than in female rats. The results show that the constitutive as well as inducible expression of CYP1A is sexually dimorphic in the Sprague-Dawley rat, with females being more responsive than males to induction by pyridine but with males being more responsive than females to induction by betaNF. The findings support the involvement of different mechanisms in CYP1A induction by pyridine and betaNF.
对成年雄性和雌性斯普拉格-道利大鼠的肺、肾和肝脏中细胞色素P450 1A1和细胞色素P450 1A2（CYP1A）的组成水平和诱导性进行了比较。通过连续两天腹腔注射吡啶（75毫克/千克/天）或β-萘黄酮（βNF；25毫克/千克/天）诱导CYP1A，然后从催化水平（通过试卤灵醚的O-脱烷基化）、蛋白质水平（通过蛋白质印迹分析）和mRNA水平（通过Northern印迹分析）进行分析。在未处理的大鼠中，CYP1A1蛋白及其mRNA仅在雌性大鼠的肺和肾中可检测到，而在雄性大鼠中未检测到，而CYP1A2蛋白及其mRNA在两种性别的大鼠肝脏中均可检测到。吡啶处理上调了雌性大鼠肺、肾和肝脏中CYP1A1的mRNA及其蛋白，上调了雄性大鼠肺和肝脏中的mRNA，但未上调蛋白。相反，吡啶诱导了雌性大鼠肝脏中CYP1A2的mRNA和蛋白，而在雄性大鼠肝脏中诱导了蛋白，但未诱导其mRNA。在所给予吡啶的血浆消除率方面未观察到性别差异。与吡啶相反，βNF诱导雄性大鼠的CYP1A蛋白、活性和mRNA水平高于雌性大鼠。结果表明，在斯普拉格-道利大鼠中，CYP1A的组成性和诱导性表达存在性别差异，雌性对吡啶诱导的反应比雄性更敏感，但雄性对βNF诱导的反应比雌性更敏感。这些发现支持了吡啶和βNF诱导CYP1A涉及不同机制。
