Abstract:
Cisplatin is a powerful chemotherapeutic drug used in cancer therapy because it can cause DNA damage, inhibit proliferating cancer cells, and induce apoptosis. Its cytotoxicity, however, is not selective for cancer cells, and protective measures against loss of DNA integrity during treatment are needed. Observational and clinical studies suggest that vitamin levels can influence chemotherapy-induced genotoxicity, but whether vitamin supplementation protects the genome during chemotherapy remains unclear. Our study explored the impact of vitamin B12 supplementation on DNA Damage Repair (DDR) mechanisms following cisplatin-induced DNA damage. Using cell culture models, we assessed DNA damage through quantitative imaging of γH2AX foci using immunofluorescence assay (IFA). Our findings revealed that vitamin B12 alone induced DNA damage foci, with higher concentrations causing more foci than lower concentrations. When B12 and cisplatin were coupled, a similar effect was seen: larger doses of B12 worsened DNA damage, while lower quantities seemed to be protective. Cisplatin-induced damage recovered in 24 hours, whereas vitamin B12-induced damage resolved within a few hours, suggesting a transient effect. Interestingly, cell cycle analysis showed a reduction in S-phase cells at high-dose vitamin B12 (100 µM), indicating potential interference with DNA replication. Despite these findings, RT-PCR analysis did not show significant changes in key DDR genes. This suggests that B12-induced DNA damage occurs through mechanisms independent of transcriptional regulation. These findings indicate that while low doses of vitamin B12 may offer some protection, excessive intake could be detrimental, emphasizing the importance of controlled vitamin supplementation.
