title: Maternal bias in mouse radiosensitivity: the role of the mitochondrial PTP.
abstract: This study investigated, at the molecular level, mitochondrial responses to radiation. In three mouse strains, we found the following: (1) mitochondrial response to calcium stress was associated with a strain's susceptibility to γ-radiation; (2) γ-radiation increased this calcium stress response in a dose-responsive manner; (3) the mitochondrial DNA (mtDNA) copy number in the liver of the radiosensitive mouse strain was significantly lower, as compared to that of the radioresistant strain; (4) adenine nucleotide translocase (ANT) mRNA copy numbers were significantly lower in the radiosensitive strain; (5) the F1 offspring (BC/C57M) of radiosensitive females mated with radioresistant males exhibited a significant difference in calcium stress response from that of the radiation-resistant strain, but the reverse cross did not exhibit this difference; and (6) only those mitochondria extracted from the livers of irradiated BC/C57M mice exhibited a heightened calcium stress response. We propose that a genetic change in ANT and a postirradiation change involving either mtDNA-encoded protein replacement or altered mtDNA association fit these data.
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA. bszhang@ufl.edu.
authors.forename: Steven Bingrong
authors.initials: SB
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: David
authors.initials: D
authors.lastname: Maguire
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: Lurong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Swarts
authors.affiliation: Department of Radiation Oncology, UF Shands Cancer Center, University of Florida, 2033 Mowry Road, Gainesville, FL, 32610, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Okunieff
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism* / Q000528:radiation effects*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D010539:Permeability; D011836:Radiation Tolerance
chemical_list: D004272:DNA, Mitochondrial; D000226:Mitochondrial ADP, ATP Translocases; D002118:Calcium