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Radiation induces aerobic glycolysis through reactive oxygen species.

Publication ,  Journal Article
Zhong, J; Rajaram, N; Brizel, DM; Frees, AE; Ramanujam, N; Batinic-Haberle, I; Dewhirst, MW
Published in: Radiother Oncol
March 2013

BACKGROUND AND PURPOSE: Although radiation induced reoxygenation has been thought to increase radiosensitivity, we have shown that its associated oxidative stress can have radioprotective effects, including stabilization of the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1 is known to regulate many of the glycolytic enzymes, thereby promoting aerobic glycolysis, which is known to promote treatment resistance. Thus, we hypothesized that reoxygenation after radiation would increase glycolysis. We previously showed that blockade of oxidative stress using a superoxide dismutase (SOD) mimic during reoxygenation can downregulate HIF-1 activity. Here we tested whether concurrent use of this drug with radiotherapy would reduce the switch to a glycolytic phenotype. MATERIALS AND METHODS: 40 mice with skin fold window chambers implanted with 4T1 mammary carcinomas were randomized into (1) no treatment, (2) radiation alone, (3) SOD mimic alone, and (4) SOD mimic with concurrent radiation. All mice were imaged on the ninth day following tumor implantation (30 h following radiation treatment) following injection of a fluorescent glucose analog, 2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl)amino]-2-deoxyglucose (2-NBDG). Hemoglobin saturation was measured by using hyperspectral imaging to quantify oxygenation state. RESULTS: Mice treated with radiation showed significantly higher 2-NBDG fluorescence compared to controls (p=0.007). Hemoglobin saturation analysis demonstrated reoxygenation following radiation, coinciding with the observed increase in glycolysis. The concurrent use of the SOD mimic with radiation demonstrated a significant reduction in 2-NBDG fluorescence compared to effects seen after radiation alone, while having no effect on reoxygenation. CONCLUSIONS: Radiation induces an increase in tumor glucose demand approximately 30 h following therapy during reoxygenation. The use of an SOD mimic can prevent the increase in aerobic glycolysis when used concurrently with radiation, without preventing reoxygenation.

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Published In

Radiother Oncol

DOI

EISSN

1879-0887

Publication Date

March 2013

Volume

106

Issue

3

Start / End Page

390 / 396

Location

Ireland

Related Subject Headings

  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Oncology & Carcinogenesis
  • Mice
  • Mammary Neoplasms, Experimental
  • Glycolysis
  • Female
  • Deoxyglucose
  • Animals
  • Aerobiosis
 

Citation

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Zhong, J., Rajaram, N., Brizel, D. M., Frees, A. E., Ramanujam, N., Batinic-Haberle, I., & Dewhirst, M. W. (2013). Radiation induces aerobic glycolysis through reactive oxygen species. Radiother Oncol, 106(3), 390–396. https://doi.org/10.1016/j.radonc.2013.02.013
Zhong, Jim, Narasimhan Rajaram, David M. Brizel, Amy E. Frees, Nirmala Ramanujam, Ines Batinic-Haberle, and Mark W. Dewhirst. “Radiation induces aerobic glycolysis through reactive oxygen species.Radiother Oncol 106, no. 3 (March 2013): 390–96. https://doi.org/10.1016/j.radonc.2013.02.013.
Zhong J, Rajaram N, Brizel DM, Frees AE, Ramanujam N, Batinic-Haberle I, et al. Radiation induces aerobic glycolysis through reactive oxygen species. Radiother Oncol. 2013 Mar;106(3):390–6.
Zhong, Jim, et al. “Radiation induces aerobic glycolysis through reactive oxygen species.Radiother Oncol, vol. 106, no. 3, Mar. 2013, pp. 390–96. Pubmed, doi:10.1016/j.radonc.2013.02.013.
Zhong J, Rajaram N, Brizel DM, Frees AE, Ramanujam N, Batinic-Haberle I, Dewhirst MW. Radiation induces aerobic glycolysis through reactive oxygen species. Radiother Oncol. 2013 Mar;106(3):390–396.
Journal cover image

Published In

Radiother Oncol

DOI

EISSN

1879-0887

Publication Date

March 2013

Volume

106

Issue

3

Start / End Page

390 / 396

Location

Ireland

Related Subject Headings

  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Oncology & Carcinogenesis
  • Mice
  • Mammary Neoplasms, Experimental
  • Glycolysis
  • Female
  • Deoxyglucose
  • Animals
  • Aerobiosis