Radioprotective effects of manganese-containing superoxide dismutase mimics on ataxia-telangiectasia cells.
Journal Article (Journal Article)
We tested several classes of antioxidant manganese compounds for radioprotective effects using human lymphoblastoid cells: six porphyrins, three salens, and two cyclic polyamines. Radioprotection was evaluated by seven assays: XTT, annexin V and propidium iodide flow cytometry analysis, gamma-H2AX immunofluorescence, the neutral comet assay, dichlorofluorescein and dihydroethidium staining, resazurin, and colony survival assay. Two compounds were most effective in protecting wild-type and A-T cells against radiation-induced damage: MnMx-2-PyP-Calbio (a mixture of differently N-methylated MnT-2-PyP+ from Calbiochem) and MnTnHex-2-PyP. MnTnHex-2-PyP protected WT cells against radiation-induced apoptosis by 58% (p = 0.04), using XTT, and A-T cells by 39% (p = 0.01), using annexin V and propidium iodide staining. MnTnHex-2-PyP protected WT cells against DNA damage by 57% (p = 0.005), using gamma-H2AX immunofluorescence, and by 30% (p < 0.01), using neutral comet assay. MnTnHex-2-PyP is more lipophilic than MnMx-2-PyP-Calbio and is also >10-fold more SOD-active; consequently it is >50-fold more potent as a radioprotectant, as supported by six of the tests employed in this study. Thus, lipophilicity and antioxidant potency correlated with the magnitude of the beneficial radioprotectant effects observed. Our results identify a new class of porphyrinic radioprotectants for the general and radiosensitive populations and may also provide a new option for treating A-T patients.
Full Text
Duke Authors
Cited Authors
- Pollard, JM; Reboucas, JS; Durazo, A; Kos, I; Fike, F; Panni, M; Gralla, EB; Valentine, JS; Batinic-Haberle, I; Gatti, RA
Published Date
- August 1, 2009
Published In
Volume / Issue
- 47 / 3
Start / End Page
- 250 - 260
PubMed ID
- 19389472
Pubmed Central ID
- PMC3592562
Electronic International Standard Serial Number (EISSN)
- 1873-4596
Digital Object Identifier (DOI)
- 10.1016/j.freeradbiomed.2009.04.018
Language
- eng
Conference Location
- United States