Combined Long-Term Effects of Metal Nanocatalysts and UVB on Human Epidermal Keratinocytes

Details

• Personal Author:
  Friend S ; Guppi S ; Kisin ER ; Shvedova AA
• Description:
  Transition metal ferrites (MFe2O4) are widely used for various industrial catalytic processes due to their extraordinary properties and stability thus representing potential human health risk. The health effects arising from exposure to nano-catalysts depend on their composition and the extent of exposure. In addition to inhalation exposure route, workers may also be exposed through dermal contact where keratinocytes are main cellular constituents of the epidermis and highly active sentinel cells. Further, the study of interactions of nanoparticles (NPs) with the skin cells, in particular after the environmental stress like UVB exposure, are essential. The aim of this study was to investigate the cytotoxicity, oxidative stress, genotoxicity, cytokine responses and potential to induce cell transformation following long-term (8 weeks) exposure of human epidermal keratinocytes (HEK) to a sub-toxic dose of two spinel ferrite NPs, NiFe2O4 or CoFe2O4, with or without UVB (2 kJ/cm2) pre-treatment. Long-term exposure to NPs caused structural alterations in cells that were enhanced by co-exposure with UVB. Significant oxidative modification of proteins - accumulation of carbonyls - was induced only by combined exposure with UVB, while an increase in lipid peroxidation products and phosphorylated H2AX protein was induced by both NPs alone and co-exposure to UVB. UVB alone caused marked amplification of the observed responses. Moreover, NPs alone induced significant changes in cell invasion (except NiFe2O4), migration and anchorage-independent growth stimulated by UVB pre-treatment. Nickel NPs, known to cause cell transformation, were used as a positive control. These findings are further supported by observed levels of cytokines/chemokines/growth factors secretion related to inflammatory and TH2-type/regulatory immune responses. Exposure to NiFe2O4 alone caused release of IL-8 and IL-12p70, while RANTES was specific only for CoFe2O4. Secretion of IL-9, IL-15, IL-17, G-CSF and MIP-1b was induced by both NPs and significantly amplified by UVB pre-treatment, while VEGF, IL-2, IL-5, IL-8, IL-12p70, GM-CSF and Eotaxin were released by cells exposed to both, NPs and UVB. Release of IL-4, RANTES and MIP-1a were unique for CoFe2O4/ UVB co-exposure. Altogether, these results clearly indicate that spinel ferrite NPs alone or combined with UVB pre-treatment can induce cytotoxicity, oxidative stress, and inflammation, and may potentially influence neoplastic-like transformation in HEK. Moreover, such effects are dependent on the composition of NPs. Further long-term studies focusing on understanding molecular mechanisms and likelihood to induce tumorigenic effects in vivo are necessary. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Occupational Health Safety Skin
• Keywords:
  Cellular Effects Cytokines Cytotoxicity Dermal Exposures Nanoparticles Skin Exposure Ultraviolet Light
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  192
• NIOSHTIC Number:
  nn:20067234
• Citation:
  Toxicologist 2023 Mar; 192(S1):500
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 62nd Annual Meeting & ToxExpo, March 19-23, 2023, Nashville, Tennessee
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e37fc0f8c4b1ac752d2143bdcfa2b8cab4e043d5c9f9e5dab2ffcf69bea8e5111e2a0146ef76766def1944b1c6b76fbc894eabef6d1890e48b2800496dd3d251
• Download URL:
  https://stacks.cdc.gov/view/cdc/231357/cdc_231357_DS1.pdf
• File Type:
  [PDF - 1.09 MB ]