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Dendro[C60]fullerene DF-1 provides radioprotection to radiosensitive mammalian cells

Abstract

In this study, the ability of the C60 fullerene derivative DF-1 to protect radiosensitive cells from the effects of high doses of gamma irradiation was examined. Earlier reports of DF-1’s lack of toxicity in these cells were confirmed, and DF-1 was also observed to protect both human lymphocytes and rat intestinal crypt cells against radiation-induced cell death. We determined that DF-1 protected both cell types against radiation-induced DNA damage, as measured by inhibition of micronucleus formation. DF-1 also reduced the levels of reactive oxygen species in the crypt cells, a unique capability of fullerenes because of their enhanced reactivity toward electron-rich species. The ability of DF-1 to protect against the cytotoxic effects of radiation was comparable to that of amifostine, another ROS-scavenging radioprotector. Interestingly, localization of fluorescently labeled DF-1 in fibroblast was observed throughout the cell. Taken together, these results suggest that DF-1 provides powerful protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, and cell death.

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Abbreviations

DCFH-DA:

2′,7′-Dichlorofluoroscein diacetate

DF-1:

Dendro[C60]fullerene-1

f-DF-1:

Fluorescently labeled df-1

FBS:

Fetal bovine serum

PHA:

Phytohemagglutinin

PBS:

Phosphate buffered saline

ROS:

Reactive oxygen species

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Acknowledgments

We would like to thank Delia Danila (University of Texas Medical School at Houston) for her expertise in covalent labeling of nanoparticles, and Tego Biosciences for providing DF-1. This research was supported by the NASA Focused Investment Group program. The research conducted by C. Theriot was supported by an appointment to the NASA Postdoctoral Program at the Johnson Space Center, administered by Oak Ridge Associated Universities through a contract with NASA. Sources of Support for Research: NASA Technology Investment Fund EXCX22008D.

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Correspondence to Honglu Wu.

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This manuscript is based on a contribution given at the “Heavy Ions in Therapy and Space Symposium 2009,” July 6–10, 2009, Cologne, Germany.

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Theriot, C.A., Casey, R.C., Moore, V.C. et al. Dendro[C60]fullerene DF-1 provides radioprotection to radiosensitive mammalian cells. Radiat Environ Biophys 49, 437–445 (2010). https://doi.org/10.1007/s00411-010-0310-4

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  • DOI: https://doi.org/10.1007/s00411-010-0310-4

Keywords

  • Fullerene
  • Zebrafish Embryo
  • Amifostine
  • Crypt Cell
  • Micronucleus Formation