Abstract
Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO2 NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO2 NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO2 NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order to explore the mechanism of protection by TiO2 NP against BaP, we performed in silico studies. BaP and other PAHs are known to enter the cell via aromatic hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12074) as compared to the docking score of BaP with AHR (4600). This indicates a preferential binding of TiO2 NP with the AHR, in case if both the TiO2 NP and BaP are present. Further, we have done the docking of BaP with the TiO2 NP bound AHR-complex (score 4710), and observed that BaP showed strong adsorption on TiO2 NP itself, and not at its original binding site (at AHR). TiO2 NPs thereby prevent the entry of BaP in to the cell via AHR and hence protect cells against the deleterious effects induced by BaP.
Highlights
IntroductionMost of the human cancers are caused due to exposure to xenobiotics including Polycyclic aromatic hydrocarbons (PAH) and they are preventable
Human exposure to xenobiotics is almost inevitable
BaP is the only Polycyclic aromatic hydrocarbons (PAH) listed in group 1 by the International agency for research on cancer [4], and has been broadly considered and constitutes the reference compound for assessing toxicity of exposure to mixtures in the toxic equivalent factors approach [5]
Summary
Most of the human cancers are caused due to exposure to xenobiotics including PAHs and they are preventable. The carcinogenic properties of BaP in particular are mostly explained by their capability to induce DNA damage. The scavenging capacities of the nanoparticles for PAH and other toxicants could be attributed to their higher affinity towards the xenobiotics due to surface chemistry, large surface area and other intrinsic properties of nanoparticles. TNT exhibits highly efficient reduction capability for most of the harmful compounds This might be related to the intrinsic properties of TNT [11]. We designed the present study in order to explore whether the discussed property of the TiO2 NPs could be exploited in the biological system to safeguard against the deleterious effects of PAHs exposure. In silico experiments were performed using bioinformatics tools, to attain insight of mechanism of protection
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