Assessment of tumor prevention in Type 1 Neurofibromatosis using a nitroxide compound

El-Hoss, Jad, Micallef, Aaron, Fairfull-Smith, Kathryn, Bottle, Steven, Little, David, & Schindeler, Aaron (2011) Assessment of tumor prevention in Type 1 Neurofibromatosis using a nitroxide compound. Free Radicals and Antioxidants, 1(3), pp. 13-18.

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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 4 μM and 40 μM 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 4 μM but not 40 μM 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.

Impact and interest:

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ID Code: 52364
Item Type: Journal Article
Refereed: Yes
Keywords: neurofibromatosis type 1, tumorigenesis, papillomas, antioxidant, nitroxide
ISSN: 2231-2536
Divisions: Past > Schools > Chemistry
Past > QUT Faculties & Divisions > Faculty of Science and Technology
Current > QUT Faculties and Divisions > Science & Engineering Faculty
Deposited On: 19 Jul 2012 06:29
Last Modified: 30 Nov 2015 00:48

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