title: UVB irradiation-enhanced zinc oxide nanoparticles-induced DNA damage and cell death in mouse skin.
abstract: UV-induced reactive oxygen species (ROS) have been implicated in photocarcinogenesis and skin aging. This is because UV-induced ROS can induce DNA damage that, if unrepaired, can lead to carcinogenesis. Sunscreens contain UV attenuators, such as organic chemical and/or physical UV filters, which can prevent all forms of damage from UV irradiation. In recent years, the effective broad-spectrum UV attenuation properties of ZnO-nanoparticles (ZnO-NPs) have made them attractive as active components in sunscreens and other personal care products. As the use of ZnO-NPs in sunscreens is on the rise, so is public concern about their safety, particularly with exposure to sunlight. Therefore, in the present study, using various experimental approaches, we investigated the possible toxic effects resulting from exposure to UVB and ZnO-NPs in primary mouse keratinocytes (PMKs) as well as in the skin of SKH-1 hairless mice. The findings of the present study demonstrated that co-exposure to UVB and ZnO-NPs: (1) translocated the ZnO-NPs into the nucleus of PMKs; (2) caused enhanced generation of ROS; (3) induced more severe DNA damage as evident by alkaline comet assay and immunocytochemistry for γ-H2AX and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and (4) subsequently caused much more pronounced cell death in PMKs. Further, to elucidate the physiological relevance of these in vitro findings, SKH-1 hairless mice were topically treated with ZnO-NPs and after 30min irradiated with UVB (50mJ/cm(2)). Interestingly, we found that co-exposure of ZnO-NPs and UVB caused increased oxidative DNA damage and cell death, indicated by immunostaining for 8-OHdG and TUNEL assay in sections of exposed mouse skin. Thus, collectively, our findings suggest that UVB exposure increases ZnO-NPs-mediated oxidative stress and oxidative damage, thereby enhancing ZnO-NPs-induced cell death.
authors.affiliation: Environmental Carcinogenesis Laboratory, Food, Drug, and Chemical Toxicology Group CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Department of Biochemistry, School of Dental Sciences, Babu Banarsi Das University (BBDU) Faizabad Road, Lucknow 226028, Uttar Pradesh, India.
authors.forename: Anu
authors.initials: A
authors.lastname: Pal
authors.affiliation: Environmental Carcinogenesis Laboratory, Food, Drug, and Chemical Toxicology Group CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Shamshad
authors.initials: S
authors.lastname: Alam
authors.affiliation: Nanomaterials Toxicology Laboratory, Nanotherapeutics and Nanomaterials Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-Indian Institute of Toxicology Research Campus, (CSIT-IITR), Lucknow 226001, Uttar Pradesh, India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Mittal
authors.affiliation: Electron Microscopy Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Arjaria
authors.affiliation: Electron Microscopy Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Jai
authors.initials: J
authors.lastname: Shankar
authors.affiliation: Animal House Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Mahadeo
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Animal House Facility, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Singh
authors.affiliation: Nanomaterials Toxicology Laboratory, Nanotherapeutics and Nanomaterials Toxicology Group, CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India; Department of Biochemistry, School of Dental Sciences, Babu Banarsi Das University (BBDU) Faizabad Road, Lucknow 226028, Uttar Pradesh, India.
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Pandey
authors.affiliation: Environmental Carcinogenesis Laboratory, Food, Drug, and Chemical Toxicology Group CSIR-Indian Institute of Toxicology Research (CSIR-IITR), Vishvigyan Bhawan, 31, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India. Electronic address: kmansari@iitr.res.in.
authors.forename: Kausar Mahmood
authors.initials: KM
authors.lastname: Ansari
mesh_terms: D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D004249:DNA Damage; D005260:Female; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D053768:Metal Nanoparticles / Q000009:adverse effects / Q000737:chemistry / Q000633:toxicity*; D051379:Mice; D018384:Oxidative Stress; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013473:Sunscreening Agents / Q000009:adverse effects / Q000737:chemistry; D014466:Ultraviolet Rays / Q000009:adverse effects*; D015034:Zinc Oxide / Q000633:toxicity*
chemical_list: D013473:Sunscreening Agents; D015034:Zinc Oxide
keywords: DNA damage; SKH-1 hairless mice; UVB radiation; Zinc oxide nanoparticles