• Modeling Mechanism：

  Ferric nitrilotriacetate (Fe-NTA) generates a large amount of reactive oxygen species (ROS) through the iron-mediated Fenton reaction, inducing oxidative stress damage in proximal renal tubular cells. Simultaneously, it induces DNA oxidative modification (generating 8-hydroxy-2'-deoxyguanosine (8-OHdG) and acrolein-modified adenosine (acrolein-dA)), leading to characteristic gene mutations (preferential mutations in G:C base pairs, mainly G:C→C:G transversions, accompanied by large deletions >1kb). Long-term damage causes abnormal regeneration of renal tubular cells and homozygous deletion of tumor suppressor genes (such as p16^INK4a), ultimately inducing renal cell carcinoma.

• Related Products：

  Ferric nitrilotriacetate (T78655)

• Modeling Method：

  Experimental Subject：

  Mice, gpt delta/C57BL/6J transgenic mice, Male, 4 weeks old

  Dosage and Administration Route：

  ① Drug preparation: Freshly prepare Ferric nitrilotriacetate solution immediately before use
  ② Administration regimen: 3 mg iron/kg Ferric nitrilotriacetate administered intraperitoneally daily for the first 3 days, with dosage increased to 5 mg iron/kg from day 4 onwards; administered 5 times weekly;
  ③ Control treatment: Control mice received no Ferric nitrilotriacetate injections, with all other housing conditions identical;

  Dosing Frequency and Duration Model：

  Days 1–3: Once daily;
  Day 4 onwards: Once daily, administered five times weekly

• Validation：

  1. Pathological markers: - Renal tubular injury: HE staining showed proximal tubular cell degeneration and necrosis (nuclear pyknosis) at 1 week, with abnormal regeneration cells (large nuclei and prominent nucleoli) appearing at 2-3 weeks; - Oxidative damage: Immunohistochemistry showed positive nuclear staining for 8-OHdG and acrolein-dA in renal tissue, with the highest expression level at 1 week; 2. Molecular markers: - Gene mutations: 6-thioguanine (6-TG) screening showed a 2.44-fold increase in point mutation frequency, and Spi⁻ screening showed a 1.72-fold increase in large fragment deletion frequency. Sequencing confirmed large fragment deletions mediated by G:C→C:G transversions and short homologous sequences near repetitive sequences; - Gene expression: deletion of the tumor suppressor gene p16^INK4a allele, and abnormal expression of genes such as annexin 2 and thioredoxin-binding protein-2.

*Precautions： After the last administration of medication to the animal 48He was executed when he was young.

*References：Jiang L,et,al. Deletion and single nucleotide substitution at G:C in the kidney of gpt delta transgenic mice after ferric nitrilotriacetate treatment. Cancer Sci. 2006 Nov;97(11):1159-67.