Intraoral Mitochondrial-Targeted GS-Nitroxide, JP4-039, Radioprotects Normal Tissue in Tumor-Bearing Radiosensitive Fancd2(-/-) (C57BL/6) Mice

Radiation Research
Ashwin ShindeJoel S Greenberger

Abstract

We evaluated normal tissue specific radioprotection of the oral cavity in radiosensitive Fanconi Anemia (FA) Fancd2(-/-) mice with orally established tumors using mitochondrial-targeted GS-nitroxide (JP4-039). Adult (10-12 weeks old) Fancd2(+/+), Fancd2(+/-) and Fancd2(-/-) mice (C57BL/6 background) and subgroups with orally established TC-1 epithelial cell tumors received a single fraction of 28 Gy or four daily fractions of 8 Gy to the head and neck. Subgroups received JP4-039 in F15 emulsion (F15/JP4-039; 0.4 mg/mouse), 4-amino-Tempo in F15 emulsion (F15/4-amino-Tempo; 0.2 mg/mouse) or F15 emulsion alone prior to each irradiation. Oral mucosa of Fancd2(-/-) mice showed baseline elevated RNA transcripts for Sod2, p53, p21 and Rad51 (all P < 0.0012) and suppressed levels of Nfkb and Tgfb, (all P < 0.0020) compared with Fancd2(+/+) mice. The oral mucosa in tumor-bearing mice of all genotypes showed decreased levels of p53 and elevated Tgfb and Gadd45a (P ≤ 0.0001 for all three genotypes). Intraoral F15/JP4-039, but not F15/4-amino-Tempo, modulated radiation-induced normal tissue transcript elevation, ameliorated mucosal ulceration and reduced the depletion of antioxidant stores in oral cavity tissue of all genotypes, but did no...Continue Reading

References

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Citations

Oct 12, 2016·ACS Central Science·Tanja KrainzPeter Wipf
Oct 25, 2016·Biochemical and Biophysical Research Communications·Xinxin SongDaolin Tang
Aug 8, 2019·Cancer·José M AmenábarChamindie Punyadeera
Jul 12, 2019·Radiation Research·Stephanie ThermozierJoel S Greenberger
Jun 19, 2018·Journal of Cell Communication and Signaling·Bagher FarhoodMasoud Najafi
Oct 27, 2018·Current Clinical Pharmacology·Keywan MortezaeeBagher Farhood
May 28, 2021·Frontiers in Oncology·Marike W van GisbergenLudwig J Dubois
Jul 3, 2021·Antioxidants·Joel S GreenbergerMichael W Epperly

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