Sustained DDB-2 and TRX Transcriptional Response of Quercetin-Treated Lymphocytes Exposed to Co-60 Radiation

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The flavonoid quercetin has been previously studied for its radioprotective and anti-cancer properties. However, none so far have described the transcriptional changes that occur in radiation-induced genes in the presence of quercetin. The objectives of the study were to demonstrate the effect of quercetin treatment on the transcription of DNA damage-binding gene (DDB-2) and endogenous antioxidant Thioredoxin (TRX) in lymphocytes after exposure to ionizing radiation and to document these transcriptional changes over a 24 h period. Peripheral blood was collected from consenting healthy donors, treated with 12.5 to 50 μM quercetin, and exposed to 2 Gy of Co-60 radiation. Total RNA was extracted from lymphocytes, reverse transcribed to cDNA and amplified by real-time PCR. Expression of genes were normalized to β-actin and expressed relative to non-irradiated control. Results showed that in the absence of quercetin treatment, cell viability was reduced to 96% at 1 h after radiation exposure, accompanied by >5-fold (5.86 ± 2.9, p < 0.05) and >2-fold (2.9 ± 0.6, p < 0.05) DDB-2 and TRX upregulation, respectively. TRX downregulation was observed in 12.5 μM quercetin– treated cells at 1 h post-irradiation (0.5 ± 0.18-fold, p < 0.05), which was sustained until 6 h (0.53 ± 0.19-fold, p < 0.05) post irradiation. DDB-2 was also downregulated to 1.8-fold with 12.5 μM treatment at 1 h post irradiation but this was not significant and until 24 h post irradiation (0.6 ± 0.09-fold, p < 0.05). Decreased radiation-induced expression of both DDB-2 and TRX was also observed as the quercetin concentration increased to 50 μM, although no significant differences were detected. These results demonstrate the sustained effect of quercetin on the transcription of radiation-induced DNA repair and anti-oxidant genes in lymphocytes, supporting the transcriptional mechanisms behind its radioprotective capability.