Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice

Qing-Shuo Zhang, Laura Eaton, Eric R. Snyder, Scott Houghtaling, James B. Mitchell, Milton Finegold, Carter Van Waes, Markus Grompe

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Fanconi anemia (FA) is a genetic disorder characterized by congenital abnormalities, bone marrow failure, and marked cancer susceptibility. FA patients have an elevated risk of developing hematologic malignancies and solid tumors. Using Fancd2-/- knockout mice as a model of FA, we examined the potential of tempol, a nitroxide antioxidant and a superoxide dismutase mimetic, as a tumor-delaying agent for solid tumors. Dietary tempol increased the mean tumor-free survival time of Fancd2-/- Trp53+/- mice by 27% (P <0.01), from 308 to 390 days, without changing the overall tumor spectrum. More strikingly, tempol delayed the onset of epithelial tumors and increased the mean epithelial tumor-free survival time by 38% (P <0.0001), from 312 to 432 days, in Fancd2-/- Trp53+/- mice. These results show that tempol can significantly delay tumor formation in Fancd2-/- Trp53+/- mice. Furthermore, tempol treatment did not adversely affect the repopulating ability of FA hematopoietic stem cells. The reduction in oxidative DNA damage in tempol-treated FA fibroblasts and mice suggests that its tumor-delaying function may be attributed to its antioxidant activity.

Original languageEnglish (US)
Pages (from-to)1601-1608
Number of pages8
JournalCancer Research
Volume68
Issue number5
DOIs
Publication statusPublished - Mar 1 2008

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Zhang, Q-S., Eaton, L., Snyder, E. R., Houghtaling, S., Mitchell, J. B., Finegold, M., ... Grompe, M. (2008). Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. Cancer Research, 68(5), 1601-1608. https://doi.org/10.1158/0008-5472.CAN-07-5186