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.
authors.affiliation: Oregon Stem Cell Center, Oregon Health and Science University, Portland, OR 97239, USA. zhangqi@ohsu.edu
authors.forename: Qing-Shuo
authors.initials: QS
authors.lastname: Zhang
authors.forename: Laura
authors.initials: L
authors.lastname: Eaton
authors.forename: Eric R
authors.initials: ER
authors.lastname: Snyder
authors.forename: Scott
authors.initials: S
authors.lastname: Houghtaling
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Milton
authors.initials: M
authors.lastname: Finegold
authors.forename: Carter
authors.initials: C
authors.lastname: Van Waes
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004249:DNA Damage; D004195:Disease Models, Animal; D018572:Disease-Free Survival; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology*; D005260:Female; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000517:prevention & control*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D013113:Spin Labels; D013482:Superoxide Dismutase; D010100:Oxygen; C001803:tempol