Metal/metal oxide nanoparticles (Me/MeO NP), e.g. nickel (Ni), cobalt (Co), nickel oxide (NiO), and cobalt oxide (Co3O4), are commercially available and used by the medical/chemical industries for a number of pharmaceutical and engineering applications. The physical nature and reactive surface properties of NPs may affect their ability to induce dermal toxicity thus causing adverse skin reactions. Although the effects of Ni and Co on skin are well known (hypersensitivity, contact dermatitis and cancer), the dermal effects of Me/MeO NPs are unknown. We hypothesize that NPs may be toxic via the metal's ability to generate reactive oxygen species, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading to inflammation. Due to the skin's susceptibility to UV radiation, it is important to address the combined effect of UVB and NPs. To test the hypothesis, the effects of Me/MeO NPs (Co and Ni) were studied in vitro and in situ using murine epidermal cells (JB6 P+/+) and an engineered human skin (EpiDerm FT). Exposure of JB6 P+/+ cells to NPs resulted in the generation of hydroxyl radicals and activation of AP-1 and NF-ęB. Co-exposure of JB6 P+/+ cells to UVB and NPs significantly accelerated accumulation of oxidative stress products, induced release of cytokines, cell damage and death. Co-exposure of engineered skin to NPs and UVB caused epidermal thickening, activation of dermal fibroblasts, accumulation of protein carbonyls, and pro-inflammatory cytokines. Altogether, these data indicate that co-exposure of dermal cells and engineered skin to UVB and Me/MeO NPs was associated with oxidative stress, and release of inflammatory mediators as compared to those treated with NPs alone. Therefore, it is imperative to assess the adverse effects of UVB when evaluating dermal toxicity of engineered NPs on skin.
Biological-effects; Cell-biology; Cellular-reactions; Chemical-composition; Chemical-hypersensitivity; Chemical-properties; Dermatitis; Dermatosis; Engineering; Exposure-assessment; Exposure-levels; Exposure-methods; Medical-research; Microbiology; Molecular-biology; Oxides; Particulates; Pharmaceutical-industry; Reaction-rates; Skin; Skin-disorders; Skin-exposure; Surface-properties
The Toxicologist. Society of Toxicology 49th Annual Meeting and ToxExpo, March 7-11, 2010, Salt Lake City, Utah