Lin Pinpin, Hu Suh-Woan, Chang Tzu-Hua
Institute of Toxicology, Chung Shan Medical University, Taichung, Taiwan.
Toxicol Sci. 2003 Jan;71(1):20-6. doi: 10.1093/toxsci/71.1.20.
The relationships between gene expression of aryl hydrocarbon receptor (AhR), aryl hydrocarbon receptor nuclear translocator (Arnt), cytochromes P4501A1 (CYP1A1), 1B1 (CYP1B1), CYP1A1, and the inducibility of CYP1A1 and CYP1B1 were determined in 32 cultivated human lymphocytes. Cytochrome P450 induction was performed by incubating lymphocytes with benzanthracene. The relative gene expression levels were determined by quantitative real-time RT-PCR assay. We found that gender is an important confounding factor for gene expression in cultivated lymphocytes. AhR, CYP1A1 and CYP1B1 levels in noninduced lymphocytes were significantly higher in female nonsmokers than in male nonsmokers (p < 0.05). Nevertheless, CYP1A1 and CYP1B1 inducibility was lower in female nonsmokers. CYP1A1 inducibility was higher in male smokers than in male nonsmokers (p < 0.05). After controlling for gender and cigarette smoking, AhR levels positively correlated with CYP1B1 levels and CYP1A1 inducibility (p < 0.01 and p = 0.03, respectively). Arnt levels also correlated with CYP1B1 levels in induced lymphocytes (p < 0.01). However, AhR levels were negatively correlated with CYP1B1 inducibility. These data indicate that AhR expression associates with individual variation of CYP1A1 inducibility and CYP1B1 expression in cultivated lymphocytes. Furthermore, gender and cigarette smoking are important confounding factors for gene expression levels in cultivated lymphocytes.
在32例培养的人淋巴细胞中,测定了芳烃受体(AhR)、芳烃受体核转运蛋白(Arnt)、细胞色素P4501A1(CYP1A1)、1B1(CYP1B1)的基因表达以及CYP1A1和CYP1B1的诱导性之间的关系。通过将淋巴细胞与苯并蒽孵育来进行细胞色素P450诱导。采用定量实时RT-PCR法测定相对基因表达水平。我们发现性别是培养淋巴细胞基因表达的一个重要混杂因素。未诱导淋巴细胞中,女性不吸烟者的AhR、CYP1A1和CYP1B1水平显著高于男性不吸烟者(p<0.05)。然而,女性不吸烟者中CYP1A1和CYP1B1的诱导性较低。男性吸烟者中CYP1A1的诱导性高于男性不吸烟者(p<0.05)。在控制性别和吸烟因素后,AhR水平与CYP1B1水平及CYP1A1诱导性呈正相关(分别为p<0.01和p = 0.03)。诱导淋巴细胞中,Arnt水平也与CYP1B1水平相关(p<0.01)。然而,AhR水平与CYP1B1诱导性呈负相关。这些数据表明,AhR表达与培养淋巴细胞中CYP1A1诱导性和CYP1B1表达的个体差异相关。此外,性别和吸烟是培养淋巴细胞基因表达水平的重要混杂因素。