title: Impact of anatase titanium dioxide nanoparticles on mutagenic and genotoxic response in Chinese hamster lung fibroblast cells (V-79): The role of cellular uptake.
abstract: The unique physico-chemical properties of nano crystalline anatase titanium dioxide nanoparticles (TiO2NPs) render them with different biological and chemical activities. Hence, it is widely used in industrial and consumer applications. Previous studies have shown the genotoxicity of TiO2NPs. However, there is a paucity of data regarding mutagenicity of these NPs. In the present study, the cellular uptake, sub-cellular localization, cytotoxicity and short term DNA interaction of TiO2NPs (1-100 μgmL-1) of diameter ranging from 12 to 25 nm on mammalian lung fibroblast cells (V-79) has been studied. The flow cytometric analysis and electron micrographs of V-79 monolayer showed the internalization of TiO2NPs in the cytoplasm with the confirmation of elemental composition through SEM/EDX analysis. TEM analysis also showed TiO2NPs induced ultra-structural changes such as swollen mitochondria and nuclear membrane disruption in V-79 cells. TiO2NPs generated free radicals, which induced indirect mutagenic and genotoxic responses. Apart from measuring the genotoxicity by Comet assay, the mutagenic potential of TiO2NPs in V-79 cells was evaluated by mammalian HGPRT gene forward mutation assay, showing a 2.98- fold increase in 6TGRHGPRT mutant frequency (*p < 0.05, **p < 0.01, ***p < 0.001) by culture plate method, which is an early indicator of potential carcinogenicity. Hence, TiO2NPs should be closely monitored and there should be a judicious use and disposal of NPs.
authors.affiliation: CSIR- Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India; Department of Biochemistry, Babu Banarasi Das University, Faizabad Road, Lucknow, Uttar Pradesh, India.
authors.forename: Abhishek Kumar
authors.initials: AK
authors.lastname: Jain
authors.affiliation: Division of Biological & Life Sciences, School of Arts & Sciences, Ahmedabad University, Ahmedabad, Gujarat, India.
authors.forename: Violet Aileen
authors.initials: VA
authors.lastname: Senapati
authors.affiliation: CSIR- Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Singh
authors.affiliation: CSIR- Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India.
authors.forename: Kavita
authors.initials: K
authors.lastname: Dubey
authors.affiliation: CSIR- Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India.
authors.forename: Renuka
authors.initials: R
authors.lastname: Maurya
authors.affiliation: CSIR- Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow, Uttar Pradesh, India. Electronic address: pandeyalok2006@gmail.com.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Pandey
mesh_terms: D000818:Animals; D020552:Comet Assay; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D053758:Nanoparticles / Q000378:metabolism / Q000633:toxicity*; D014025:Titanium / Q000378:metabolism / Q000633:toxicity*
chemical_list: D009153:Mutagens; C009495:titanium dioxide; D014025:Titanium
keywords: Cellular uptake; Energy dispersive X-ray spectroscopy; Forward mutation; Hypoxanthine guanine phosphoribosyl transferase; Reactive oxygen species generation