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 language | English (US) |
|---|---|
| Pages (from-to) | 1601-1608 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 1 2008 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. / Zhang, Qing-Shuo; Eaton, Laura; Snyder, Eric R.; Houghtaling, Scott; Mitchell, James B.; Finegold, Milton; Van Waes, Carter; Grompe, Markus.
In: Cancer Research, Vol. 68, No. 5, 01.03.2008, p. 1601-1608.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice
AU - Zhang, Qing-Shuo
AU - Eaton, Laura
AU - Snyder, Eric R.
AU - Houghtaling, Scott
AU - Mitchell, James B.
AU - Finegold, Milton
AU - Van Waes, Carter
AU - Grompe, Markus
PY - 2008/3/1
Y1 - 2008/3/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=40449120459&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-5186
DO - 10.1158/0008-5472.CAN-07-5186
M3 - Article
C2 - 18316625
AN - SCOPUS:40449120459
VL - 68
SP - 1601
EP - 1608
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 5
ER -