Nickel Nanoparticles Induce Cell Transformation Through DNA Damage and Repair Defects

Strategic Insights -

Research conducted by Qunwei Zhang and colleagues at the University of Louisville has revealed the mechanisms underlying nickel nanoparticle-induced cell malignant transformation. The study found that nickel nanoparticles (Nano-Ni) cause DNA damage at both in vitro and in vivo settings, leading to dysregulation of the HIF-1 alpha/miR-210/Rad52 pathway. This pathway plays a crucial role in DNA repair, and its dysregulation can lead to genomic instability and ultimately cell transformation. The study also showed that long-term low-dose exposure to Nano-Ni can lead to cell malignant transformation, and that augmentation of Rad52 expression significantly reduces Nano-Ni-induced cell transformation.

Key Takeaways:

  • Nickel nanoparticles (Nano-Ni) cause DNA damage at both in vitro and in vivo settings, leading to dysregulation of the HIF-1 alpha/miR-210/Rad52 pathway.
  • The HIF-1 alpha/miR-210/Rad52 pathway plays a crucial role in DNA repair, and its dysregulation can lead to genomic instability and ultimately cell transformation.
  • Long-term low-dose exposure to Nano-Ni can lead to cell malignant transformation.
  • Augmentation of Rad52 expression significantly reduces Nano-Ni-induced cell transformation.
  • The study used immortalized normal human bronchial epithelial cells BEAS-2B to observe the effects of Nano-Ni on DNA damage response (DDR)-associated proteins and the HIF-1 alpha/miR-210/Rad52 pathway.
  • The researchers used a Hsp90 inhibitor, HIF-1 alpha knock-out cells, and a miR-210 inhibitor to determine whether Nano-Ni-induced Rad52 down-regulation was through HIF-1 alpha nuclear accumulation and miR-210 up-regulation.
  • The study also investigated Nano-Ni-exposure-induced DNA damage and dysregulation of the HIF-1 alpha/miR-210/Rad52 pathway in vivo by intratracheal instillation of Nano-Ni in gpt delta transgenic mice.

Statistics:

  • Nickel nanoparticles were tested at doses of 0, 10, 20, and 30 μg/mL.
  • The researchers used a time-response study, with cells treated with Nano-Ni for 0, 3, 6, 12, and 24 hours.
  • Long-term exposure studies were conducted for 21 cycles (approximately 150 days) at doses of 0.25 and 0.5 μg/mL.
  • The study found increased immunostaining of cell proliferation markers Ki-67 and PCNA in bronchiolar epithelial cells and hyperplastic pneumocytes in mouse lungs at day 7 and day 42 after Nano-Ni exposure.
  • The study also found that Nano-Ni exposure did not cause increased gpt mutant frequency, but did lead to certain DNA mutations, such as base substitution and small base insertions/deletions.

Sources:

  • Qunwei Zhang, Yiqun Mo, Yue Zhang, Yuanbao Zhang, Jiali Yuan, and Luke Mo. Nickel Nanoparticle-induced Cell Transformation: Involvement of Dna Damage and Dna Repair Defect Through Hif-1 Alpha/mir-210/rad52 Pathway. Journal of Nanobiotechnology, 2021;19(1).
  • University of Louisville, School of Public Health and Information Sciences, Dept. of Environmental and Occupational Health Sciences, 485 E Gray St, Louisville, KY 40202, United States.
  • Biotech Week. NewsRx. Data on Nanoparticles Described by Researchers at University of Louisville (Nickel Nanoparticle-induced Cell Transformation: Involvement of Dna Damage and Dna Repair Defect Through Hif-1 Alpha/mir-210/rad52 Pathway). December 22, 2021; p 599.