Titanium dioxide nanoparticles provide protection against polycyclic aromatic hydrocarbon BaP and chrysene-induced perturbation of DNA repair machinery: A computational biology approach.
We examined the interaction of polycyclic hydrocarbons (PAHs) like benzo-α-pyrene (BaP), chrysene, and their metabolites 7,8-dihydro-7,8-dihydroxybenzo(a)pyrene,9,10-oxide (BPDE) and chrysene 1,2-diol-3,4-epoxide-2 (CDE), with the enzymes involved in DNA repair. We investigated interaction of 120 enzymes with PAHs and screened out 40 probable targets among DNA repair enzymes, on the basis of higher binding energy than positive control. Out of which, 20 enzymes lose their function in the presence of BaP, chrysene, and their metabolites, which may fetter DNA repair pathways resulting in damage accumulation and finally leading to cancer formation. We propose the use of nanoparticles as a guardian against the PAH's induced toxicity. PAHs enter the cell via aryl hydrocarbon receptor (AHR). TiO2 NP showed a much higher docking score with AHR (12,074) as compared with BaP and chrysene with AHR (4,600 and 4,186, respectively), indicating a preferential binding of TiO2 NP with the AHR. Further, docking of BaP and chrysene with the TiO2 NP bound AHR complex revealed their strong adsorption on TiO2 NP itself, and not on their original binding site (at AHR). TiO2 NPs thereby prevent the entry of PAHs into the cell via AHR and hence protect cells against the deleterious effects induced by PAHs.
Environmental Carcinogenesis and Toxicoinformatics Laboratory, Department of Bioengineering & Biosciences, Integral University, Lucknow, India.
Anupam
A
Dhasmana
College of Applied Medical Sciences, Buraydah Colleges, Al Qassim-Buraydah King Abdul Aziz Road, East Qassim University, Buraydah, Kingdom of Saudi Arabia.
Qazi Mohd Sajid
QM
Jamal
Developmental Toxicology Division, Indian Institute of Toxicology Research, CSIR, Lucknow, India.
Richa
R
Gupta
Environmental Carcinogenesis and Toxicoinformatics Laboratory, Department of Bioengineering & Biosciences, Integral University, Lucknow, India.
Mohd Haris
MH
Siddiqui
Department of Environmental Science, University of Eastern Finland, Kuopio, Finland.
Kavindra Kumar
KK
Kesari
Department of Biotechnology, Ministry of Science and Technology, New Delhi, India.
Gulshan
G
Wadhwa
Department of Clinical Nutritions, College of Applied Medical Sciences, University of Hail, Hail, Kingdom of Saudi Arabia.
Saif
S
Khan
Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.
Shafiul
S
Haque
Environmental Carcinogenesis and Toxicoinformatics Laboratory, Department of Bioengineering & Biosciences, Integral University, Lucknow, India.
Mohtashim
M
Lohani
D001580:Benzopyrenes / Q000633:toxicity*; D002911:Chrysenes / Q000633:toxicity*; D019295:Computational Biology; D004260:DNA Repair / Q000187:drug effects*; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D053758:Nanoparticles; D011487:Protein Conformation; D014025:Titanium / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*
D001580:Benzopyrenes; D002911:Chrysenes; C031180:chrysene; C009495:titanium dioxide; D014025:Titanium; D045643:DNA Repair Enzymes
DNA damage and repair; PAHs; TiO2 NP; cancer; molecular docking