Dhasmana Anupam, Jamal Qazi Mohd Sajid, Gupta Richa, Siddiqui Mohd Haris, Kesari Kavindra Kumar, Wadhwa Gulshan, Khan Saif, Haque Shafiul, Lohani Mohtashim
Environmental Carcinogenesis and Toxicoinformatics Laboratory, Department of Bioengineering & Biosciences, Integral University, Lucknow, India.
College of Applied Medical Sciences, Buraydah Colleges, Al Qassim-Buraydah King Abdul Aziz Road, East Qassim University, Buraydah, Kingdom of Saudi Arabia.
Biotechnol Appl Biochem. 2016 Jul;63(4):497-513. doi: 10.1002/bab.1388. Epub 2015 Dec 31.
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.
我们研究了多环芳烃（PAHs）如苯并-α-芘（BaP）、屈及其代谢产物7,8-二氢-7,8-二羟基苯并(a)芘-9,10-氧化物（BPDE）和屈1,2-二醇-3,4-环氧化物-2（CDE）与参与DNA修复的酶之间的相互作用。我们调查了120种酶与PAHs的相互作用，并基于比阳性对照更高的结合能，从DNA修复酶中筛选出40个可能的靶点。其中，20种酶在BaP、屈及其代谢产物存在的情况下失去功能，这可能会阻碍DNA修复途径，导致损伤积累，最终引发癌症形成。我们建议使用纳米颗粒作为抵御PAH诱导毒性的守护者。PAHs通过芳烃受体（AHR）进入细胞。与BaP和屈与AHR的对接分数（分别为4,600和4,186）相比，TiO2纳米颗粒与AHR的对接分数更高（12,074），表明TiO2纳米颗粒与AHR具有优先结合。此外，BaP和屈与TiO2纳米颗粒结合的AHR复合物的对接显示，它们强烈吸附在TiO2纳米颗粒本身，而不是其原始结合位点（在AHR处）。因此，TiO2纳米颗粒可防止PAHs通过AHR进入细胞，从而保护细胞免受PAHs诱导的有害影响。
