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    Free Radicals and AntioxidantsNOW IN
    Article

    Assessment of tumor Prevention in type 1 neurofibromatosis using a nitroxide compound

    Jad El-Hoss1,2★, Aaron S. Micallef3, Kathryn E. Fairfull-Smith4, Steven E. Bottle4, David G. Little1,2, Aaron Schindeler1,2★ Corresponding author

    1. 1Orthopaedic Research & Biotechnology Unit, The Children’s Hospital at Westmead, Sydney, Australia.
    2. 2Discipline of Paediatrics and Child Health, Faculty of Medicine, University of Sydney, Sydney, Australia.
    3. 3Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia.
    4. 4ARC Centre of Excellence for Free Radical Chemistry and Biotechnology, Chemistry Discipline, Faculty of Science and Technology, Queensland University of Technology, Brisbane, Australia.

    CORRESPONDENCE

    Jad El-Hoss

    Orthopaedic Research & Biotechnology Unit, The Children’s Hospital at Westmead, Sydney, Australia.

    jad.elhoss@sydney.edu.au

    Volume 1, Issue 3 · pp. 13–18 · PUBLISHED · DOI: 10.5530/ax.2011.3.3

    View on Free Rad. Antiox. original site ↗

    ABSTRACT

    Background:Type 1 Neurofibromatosis (NF1) is a genetic disorder linked to mutations of the NF1 gene. Clinical symptoms are varied, but hallmark features of the disease include skin pigmentation anomalies (café au lait macules, skinfold freckling) and dermal neurofibromas. Method: These dermal manifestations of NF1 have previously been reported in a mouse model where Nf1+/- mice are topically treated with dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol- 13-acetate (TPA). We adopted this mouse model to test the protective effects of a nitroxide antioxidant, 5-carboxy-1,1,3,3- tetramethylisoindolin-2-yloxyl (CTMIO). Antioxidants have previously been shown to increase longevity in nf1-deficient fruitflies. Doses of 4µM and 40µM CTMIO provided ad libitum in drinking water were given to Nf1-deficient mice. Results: Consistent with previous reports, Nf1-deficient mice showed a 4.7-fold increase in papilloma formation (P < 0.036). However, neither dose of CTMIO had any significant affect on papilloma formation. A non-significant decrease in skin pigmentation abnormalities was seen with 4µM but not 40µM CTMIO. Subsequent analysis of genomic DNA isolated from papillomas indicated that DMBA/TPA induced tumors did not exhibit a local loss of heterozygosity (LOH) at the Nf1 locus. Conclusion: These data reveal that oral antioxidant therapy with CTMIO does not reduce tumor formation in a multistage cancer model, but also that this model does not feature LOH for Nf1.

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      El-Hoss, J., Micallef, A. S., Fairfull-Smith, K. E., Bottle, S. E., Little, D. G., & Schindeler, A. (). Assessment of tumor Prevention in type 1 neurofibromatosis using a nitroxide compound. Free Radicals and Antioxidants, 1(3), 13–18. https://doi.org/10.5530/ax.2011.3.3