title: Mitochondrial DNA and functional investigations into the radiosensitivity of four mouse strains.
abstract: We investigated whether genetic radiosensitivity-related changes in mtDNA/nDNA ratios are significant to mitochondrial 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, and mitochondria were isolated. Mitochondrial oxygen consumption, ROS, and calcium-induced mitochondrial swelling were measured. Radiation influenced strain-specific 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 mice were significantly more sensitive to calcium overload than mitochondria from C57BL/6 mice. Maternal input partially influenced the recovery effect of radiation on calcium-induced mitochondrial swelling in F1 hybrids; the hybrid with 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.
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Steven B
authors.initials: SB
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: David
authors.initials: D
authors.lastname: Maguire
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Shanmin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Casey-Sawicki
authors.affiliation: First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350108, China.
authors.forename: Deping
authors.initials: D
authors.lastname: Han
authors.affiliation: Institute of Digestive Diseases, Zhengzhou University, Henan 45001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Liangjie
authors.initials: L
authors.lastname: Yin
authors.affiliation: Department of Cardiovascular Diseases, Hospital of Fujian Province, Fuzhou 350004, China.
authors.forename: Yongson
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Physiology, Shanghai University of Sport, Shanghai 100044, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350108, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Radiobiology, National Academy of Sciences of Belarus, 220072 Gomel, Belarus.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Litvinchuk
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Zhenhuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Swarts
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Sadasivan
authors.initials: S
authors.lastname: Vidyasagar
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, University of Florida Shands Cancer Center, 2033 Mowry Road, P.O. Box 103633, Gainesville, FL 32610, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff