Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients.
Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 µg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.
Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Navrangpura, Ahmedabad 380009, Gujarat, India Department of Biotechnology, Integral University, Dasauli, P.O. Bas-ha Kursi Road, Lucknow 226026, India.
Ashutosh
A
Kumar
Division of Medical Sciences, School of Life Sciences, University of Bradford, Richmond Road, West Yorkshire, Bradford BD7 1DP, UK.
Mojgan
M
Najafzadeh
Bradford Royal Infirmary, Duckworth Lane, Bradford BD9 6RJ, UK.
Badie K
BK
Jacob
Institute of Life Sciences, School of Science and Technology, Ahmedabad University, University Road, Navrangpura, Ahmedabad 380009, Gujarat, India Nanomaterial Toxicology Group, CSIR-Indian Institute of Toxicology Research, Mahatma Gandhi Marg, P.O. Box 80, Lucknow 226001, Uttar Pradesh, India alok.dhawan@ahduni.edu.in.
Alok
A
Dhawan
Division of Medical Sciences, School of Life Sciences, University of Bradford, Richmond Road, West Yorkshire, Bradford BD7 1DP, UK.
Diana
D
Anderson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D008875:Middle Aged; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015034:Zinc Oxide / Q000633:toxicity*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D048031:JNK Mitogen-Activated Protein Kinases; D016283:Proto-Oncogene Proteins p21(ras); D015034:Zinc Oxide