1. Mitochondrial DNA and Functional Investigations into the Radiosensitivity of Four Mouse Strains.
- Author
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Zhang, Steven B., Maguire, David, Mei Zhang, Yeping Tian, Shanmin Yang, Amy Zhang, Casey-Sawicki, Katherine, Deping Han, Jun Ma, Liangjie Yin, Yongson Guo, Xiaohui Wang, Chun Chen, Litvinchuk, Alexandra, Zhenhuan Zhang, Swarts, Steven, Vidyasagar, Sadasivan, Lurong Zhang, and Okunieff, Paul
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MITOCHONDRIAL DNA , *RADIATION damage , *HISTONES , *CELL physiology , *TOTAL body irradiation - Abstract
We investigated whether genetic radiosensitivity-related changes inmtDNA/nDNA ratios are significant tomitochondrial function and if a material effect on mtDNA content and function exists. BALB/c (radiosensitive), C57BL/6 (radioresistant), and F1 hybrid mouse strains were exposed to total body irradiation. Hepatic genomic DNA was extracted, andmitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strainspecific survival in vivo. F1 hybrid survival was influenced by maternal input. Changes in mitochondrial content corresponded to survival in vivo among the 4 strains. Calcium-induced mitochondrial swelling was strain dependent. Isolated mitochondria from BALB/c micewere significantlymore sensitive to calciumoverload thanmitochondria fromC57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-inducedmitochondrial swelling in F1 hybrids; the hybridwith a radiosensitive maternal lineage exhibited a lower rate of recovery. Hybrids had a survival rate that was biased toward maternal input. mtDNA content and mitochondrial permeability transition pores (MPTP)measured in these strains before irradiation reflected a dominant input from the parent. After irradiation, the MPTP opened sooner in radiosensitive and hybrid strains, likely triggering intrinsic apoptotic pathways. These findings have important implications for translation into predictors of radiation sensitivity/resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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