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
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice'. Together they form a unique fingerprint.

  • Cite this

    Zhang, Q. S., Eaton, L., Snyder, E. R., Houghtaling, S., Mitchell, J. B., Finegold, M., Van Waes, C., & 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