Oxidative damage to DNA, expression of Mt-1, and activation of repair mechanisms induced by vanadium trioxide in cultures of human lymphocytes

• DOI: 10.1016/j.toxrep.2025.101909
• Publication Date: 2025-01-13T16:52:00Z
• Authors: V.A. Alcántara-Mejía; A.A. Beltrán-Flores; R.A. Mateos-Nava; L. Álvarez-Barrera; I.U. Bahena-Ocampo; E. Santiago-Osorio; E. Bonilla-González; J.J. Rodríguez-Me...
• Keywords: BER; ATM; RA1190-1270; Toxicology. Poisons; Protein expression; Fpg-modified comet assay; NHEJ; Article; QPCR

Vanadium (V) has garnered attention due to its pharmacological properties; however, toxic effects have also been documented. Among the vanadium compounds that are found in environment, trioxide (V2O3) attracted interest because of impact on biomolecules such as DNA, RNA, and proteins. However, precise mechanism action remains unclear, although it is suspected be related oxidative stress. Therefore, this study aimed determine mechanisms involved DNA damage associated cellular response pathways. Primary cultures human lymphocytes were exposed 2, 4, 8, or 16 µg/mL V2O3. oxidized bases was evaluated via a comet assay. The expression levels sensor proteins (ATM ATR) determined Western blotting, mRNA metallothionein 1 (Mt-1) genes repair (OGG1, APE1, XPB, XPD, MRE11, RAD50, Ku70, Ku80) estimated RT-PCR qPCR. results showed V2O3 an oxidant responsible for through bases, demonstrated by increased migration presence FPG enzyme. At molecular level, treatment ATM protein expression. In terms expression, overexpression Mt-1, OGG1, Ku80 observed. This finding suggests primarily repaired two mechanisms: base excision (BER) nonhomologous end joining (NHEJ). conclusion, one involves oxidation nitrogenous activation sensors (such ATMs), Mt-1 part antioxidant mitigate V facilitate pathways (including BER NHEJ).