Organ-specific responses of total body irradiated doxycycline-inducible manganese superoxide dismutase Tet/Tet mice.
OBJECTIVE
We evaluated doxycycline-inducible manganese superoxide dismutase (MnSOD(tet/tet)) mice after 9.25 Gy total-body irradiation (TBI) or 20 Gy thoracic irradiation.


METHODS
Six-week-old MnSOD(tet/tet) or control C57BL/6NHsd mice on or off doxycycline (doxy) in food received 9.25 Gy TBI, were sacrificed at day 19 and bone marrow, brain, esophagus, heart, intestine, kidney, liver, lung, spleen and tongue harvested, total RNAs extracted and transcripts for irradiation response genes quantitated by real time-polymerase chain reaction (RT-PCR).


RESULTS
MnSOD(tet/tet) mice only survived with daily injections of doxy beginning 5 days after birth until weaning, at which time they were placed on food containing doxy. Manganese superoxide dismutase (MnSOD) transcript levels were reduced in all tissues except the lung. Adult mice survived with low MnSOD levels, but induced by doxy or TBI. Thoracic-irradiated MnSOD(tet/tet) mice survived past day 120.


CONCLUSIONS
MnSOD(tet/tet) mice should be valuable for elucidating the role of MnSOD in growth and irradiation response.
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
Byung Han
BH
Rhieu
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
Ashwin
A
Shinde
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
Michael W
MW
Epperly
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
Tracy
T
Dixon
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A.
Hong
H
Wang
Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA, U.S.A.
Richard
R
Chaillet
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, U.S.A. greenbergerjs@upmc.edu.
Joel S
JS
Greenberger
D000818:Animals; D004318:Doxycycline / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity / Q000235:genetics; D010641:Phenotype; D013482:Superoxide Dismutase / Q000235:genetics*; D014158:Transcription, Genetic; D014916:Whole-Body Irradiation
D013482:Superoxide Dismutase; D004318:Doxycycline
MnSOD; doxycycline-induction; total body irradiation