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 Citations (Scopus)

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

Fingerprint

Fanconi Anemia
Neoplasms
Antioxidants
tempol
Inborn Genetic Diseases
Survival
Hematologic Neoplasms
Hematopoietic Stem Cells
Knockout Mice
DNA Damage
Superoxide Dismutase
Fibroblasts
Bone Marrow

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

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 journalArticle

Zhang, Q-S, Eaton, L, Snyder, ER, Houghtaling, S, Mitchell, JB, Finegold, M, Van Waes, C & Grompe, M 2008, 'Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice', Cancer Research, vol. 68, no. 5, pp. 1601-1608. https://doi.org/10.1158/0008-5472.CAN-07-5186
Zhang Q-S, Eaton L, Snyder ER, Houghtaling S, Mitchell JB, Finegold M et al. Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. Cancer Research. 2008 Mar 1;68(5):1601-1608. https://doi.org/10.1158/0008-5472.CAN-07-5186
Zhang, Qing-Shuo ; Eaton, Laura ; Snyder, Eric R. ; Houghtaling, Scott ; Mitchell, James B. ; Finegold, Milton ; Van Waes, Carter ; Grompe, Markus. / Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice. In: Cancer Research. 2008 ; Vol. 68, No. 5. pp. 1601-1608.
@article{b6b38b1245d4493fa764245cfde3845a,
title = "Tempol protects against oxidative damage and delays epithelial tumor onset in Fanconi anemia mice",
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.",
author = "Qing-Shuo Zhang and Laura Eaton and Snyder, {Eric R.} and Scott Houghtaling and Mitchell, {James B.} and Milton Finegold and {Van Waes}, Carter and Markus Grompe",
year = "2008",
month = "3",
day = "1",
doi = "10.1158/0008-5472.CAN-07-5186",
language = "English (US)",
volume = "68",
pages = "1601--1608",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=40449120459&partnerID=8YFLogxK

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 -