Potential toxicity of quercetin: The repression of mitochondrial copy number via decreased POLG expression and excessive TFAM expression in irradiated murine bone marrow

The cytotoxicity of quercetin is not well understood. Using an ICR murine model, we unexpectedly found that mice exposed to 7 Gy total body irradiation (TBI) exhibited general in vivo toxicity after receiving quercetin (100 mg/kg PO), whereas this result was not observed in mice that received TBI only. In order to understand the involvement of alterations in mitochondrial biogenesis, we used a real-time qPCR to analyze the mitochondrial DNA copy number (mtDNAcn) by amplifying the MTRNR1 (12S rRNA) gene in murine bone marrow. We also utilized reverse transcription qPCR to determine the mRNA amounts transcribed from the polymerase gamma (POLG), POLG2, and mammalian mitochondrial transcription factor A (TFAM) genes in the tissue. In the mice exposed to TBI combined with quercetin, we found: (1) the radiation-induced increase of mtDNAcn was inhibited with a concurrent significant decrease in POLG expression; (2) TFAM expression was significantly increased; and (3) the expression of POLG2 was not influenced by the treatments. These data suggest that the overall toxicity was in part associated with the decrease in mtDNAcn, an effect apparently caused by the inhibition of POLG expression and overexpression of TFAM; unaltered POLG2 expression did not seem to contribute to toxicity.