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. At 12 h after irradiation, the content of cf-nDNA and cf-mtDNA in the urine of young rats was increased by 200% and 460%, respectively, relative to the control, whereas in the urine of aged rats, it was 250% and 720% higher. After 6 h following metformin administration, the amount of cf-nDNA and cf-mtDNA in the urine of young rats was elevated by 25% and 55% and by 50% and 160% in the urine of aged rats. Thus, these preliminary data suggest that X-rays and metformin cause a significant increase of cf-DNA in the urine of older rats caused by the active cell death in tissues. These results also suggest that metformin possibly initiates the death of the cells containing structural and functional abnormalities.