Ultrafine Particles of Diesel Exhaust Induces Cytochrome P450 1A1 Mediated Oxidative Stress and DNA Damage in Cultured Blood and Lung Cells

Attempts were made to investigate the role of cytochrome P450 1A1 (CYP1A1) on similarities in the generation of reactive oxygen species (ROS) and DNA damage in IM9, a human B lymphoblastic cell line with A549, the human lung adenocarcinoma epithelial cell line on exposure of diesel exhaust particles (DEP). A suspension of ultrafine particles (< 0.2 μM) of DEP (1mg/ml) in DMEM-F12 medium, at a concentration range of 1-100 μg/ml, was added to the cells for 6-48h. Expression studies revealed that DEP induced similar increase in the expression of CYP1A1, generation of ROS and DNA damage in both the cells. Pre-incubation with 3-methylcholanthrene (MC), a CYP1A1 inducer resulted in higher magnitude of induction of CYP1A1, ROS and DNA damage. This synergistic effect was lowered when α-naphthoflavone (α-NF), an inhibitor of CYP1A1 catalysed reactions, was added to these cells. Though the magnitude of alterations was lower in IM9 cells when compared to A549 cells, similarities in the alterations in blood and lungs cells has further suggested that blood lymphocytes can be used as a surrogate to monitor toxicity of vehicular emissions