Metformin prolongs survival rate in mice and causes increased excretion of cell-free DNA in the urine of X-irradiated rats.

An antidiabetic drug metformin has anticarcinogenic and geroprotective effects and has been used in combination with radiation cancer therapy. The present work is devoted to the study of the effect of metformin on survival in mice, the frequency of micronuclei in mouse bone marrow cells and excretion of cell-free nuclear and mitochondrial DNA in the urine of X-ray-exposed rats. The survival rate and the frequency of micronuclei in mice and excretion of DNA into rat urine were determined after administration of the drug before and after irradiation of animals.

X-rays and metformin cause increased urinary excretion of cell-free nuclear and mitochondrial DNA in aged rats.

Activation of cell death in mammals can be assessed by an increase of an amount of cell-free DNA (cf-DNA) in urine or plasma. We investigated the excretion of cf nuclear DNA (nDNA) and cf mitochondrial DNA (mtDNA) in the urine of rats 3 and 24 months in age after X-irradiation and metformin administration. Analyses showed that prior to treatment, the amount of cf-nDNA was 40% higher and cf-mtDNA was 50% higher in the urine of aged rats compared to that of young animals.

Cell-free DNA in the urine of rats exposed to ionizing radiation.

Investigation of cell-free DNA (cf-DNA) in body fluids, as a potential biomarker for assessing the effect of ionizing radiation on the organism, is of considerable interest. We investigated changes in the contents of cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) in the urine of X-ray-exposed rats. Assays of cf-mtDNA and cf-nDNA were performed by a real-time PCR in rat urine collected before and after irradiation of animals with doses of 3 and 5 Gy.