Developmental Toxicology Division, Indian Institute of Toxicology Research (IITR), CSIR, MG Marg, Lucknow, UP, India.
Mutat Res. 2009 Nov 2;670(1-2):74-8. doi: 10.1016/j.mrfmmm.2009.07.006. Epub 2009 Jul 24.
To develop blood lymphocyte cytochrome P450 1A1 (CYP1A1) expression as a surrogate for monitoring tissue expression for polycyclic aromatic hydrocarbon (PAH) induced toxicity, the present study attempted to characterize CYP1A1 mRNA expression and its associated catalytic activity in freshly prepared blood lymphocytes isolated from healthy controls and patients suffering from tobacco induced lung cancer. Human blood lymphocytes were found to express CYP1A1 mRNA and significant activity of 7-ethoxyresorufin-O-deethylase (EROD). Significant increase in the activity of EROD and CYP1A1 mRNA was observed in blood lymphocytes isolated from patients suffering from lung cancer. Further, controls with variant genotypes of CYP1A1 (Msp1 or Ile/Val polymorphism) exhibited significant increase in the enzyme activity associated with an increase in CYP1A1 mRNA expression when compared to the controls with wild type genotype. Patients with variant genotypes of CYP1A1 also exhibited much greater increase in the blood lymphocyte CYP1A1 mRNA expression and EROD activity when compared to controls or patients with wild type genotype. Our data thus provides evidence of CYP1A1 expression in freshly isolated blood lymphocytes and differences in reactivity in individuals with variant genotypes of CYP1A1, suggesting that blood lymphocyte CYP1A1 expression profile could help in identifying individuals at risk to environment induced lung cancer.
为了将血液淋巴细胞细胞色素 P450 1A1（CYP1A1）的表达发展为监测多环芳烃（PAH）诱导的毒性的组织表达的替代物，本研究试图描述从健康对照者和患有烟草诱导的肺癌的患者中分离的新鲜血液淋巴细胞中 CYP1A1 mRNA 表达及其相关的催化活性。发现人血液淋巴细胞表达 CYP1A1 mRNA 和 7-乙氧基Resorufin-O-脱乙基酶（EROD）的显著活性。从患有肺癌的患者中分离的血液淋巴细胞中观察到 EROD 和 CYP1A1 mRNA 的活性显著增加。此外，与野生型基因型相比，具有 CYP1A1（Msp1 或 Ile/Val 多态性）变异基因型的对照者的酶活性与 CYP1A1 mRNA 表达的增加呈显著相关。与野生型基因型的对照者或患者相比，具有 CYP1A1 变异基因型的患者的血液淋巴细胞 CYP1A1 mRNA 表达和 EROD 活性也有更大的增加。因此，我们的数据提供了在新鲜分离的血液淋巴细胞中 CYP1A1 表达的证据，以及具有 CYP1A1 变异基因型的个体反应性的差异，这表明血液淋巴细胞 CYP1A1 表达谱可能有助于识别易患环境诱导性肺癌的个体。
