Radiation and a metalloporphyrin radioprotectant in a mouse prostate tumor model.
BACKGROUND
Antioxidants have the potential to protect normal tissues against radiation-induced damage, but must not protect tumor cells during radiotherapy. The major objectives were to determine whether a metalloporphyrin antioxidant affects prostate tumor response to radiation and identify possible mechanisms of interaction.


METHODS
C57BL/6 mice with RM-9 tumor were treated with manganese (III) meso-tetrakis (1,3-diethylimidazolium-2-yl) porphyrin (MnTDE-2-ImP) and 10 gray (Gy) radiation. Tumor volume was quantified and a subset/group was evaluated for hypoxia-inducible factor-1alpha (HIF-1alpha), bone marrow-derived cell populations and cytokines.


RESULTS
The addition of MnTDE-2-ImP transiently increased tumor response compared to radiation alone. The group receiving drug plus radiation had reduced intratumoral HIF-1alpha and decreased capacity to secrete TNF-alpha, whereas production of IL-4 was increased. There were no toxicities associated with combination treatment.


CONCLUSIONS
The results demonstrate that MnTDE-2-ImP did not protect the RM-9 prostate tumor against radiation; instead, radiation effectiveness was modestly increased. Possible mechanisms include reduction of radiation-induced HIF-1alpha and an altered cytokine profile.
Gridley
Daila S
DS
Departments of Radiation Medicine, Loma Linda University and Medical Center, Loma Linda, CA 92354, USA. dgridley@dominion.llumc.edu
Makinde
Adeola Y
AY
Luo
Xian
X
Rizvi
Asma
A
Crapo
James D
JD
Dewhirst
Mark W
MW
Moeller
Benjamin J
BJ
Pearlstein
Robert D
RD
Slater
James M
JM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D001835:Body Weight / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects / Q000528:radiation effects; D007958:Leukocyte Count; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000532:radiotherapy*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000033:anatomy & histology / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D013601:T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects
C472668:AEOL 10150; D000975:Antioxidants; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008665:Metalloporphyrins; D011837:Radiation-Protective Agents