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Title: Radiosensitization of mouse skin by oxygen and depletion of glutathione

Abstract

To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O{sub 2} in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediated levels of GSH depletion. In mice exposed to 100% O{sub 2}, a significant component of skin radiosensitivity was due to diffusion of oxygen directly through the skin. Pentobarbitone anesthesia radiosensitized skin in mice exposed to 100% O{sub 2} by a factor of 1.2, but did not further sensitize skin in mice exposed to carbogen. Glutathione levels andmore » the local oxygen tension at the time of irradiation were important determinants of mouse foot skin radiosensitivity. The extent to which GSH levels altered the radiosensitivity of skin was critically dependent on the local oxygen tension. These results have significant implications for potential clinical applications of GSH depletion. 53 refs., 7 figs., 2 tabs.« less

Authors:
; ;  [1]
  1. Gray Lab., Middlesex (United Kingdom); and others
Publication Date:
OSTI Identifier:
437130
Resource Type:
Journal Article
Journal Name:
International Journal of Radiation Oncology, Biology and Physics
Additional Journal Information:
Journal Volume: 33; Journal Issue: 2; Other Information: PBD: 30 Sep 1995
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; 56 BIOLOGY AND MEDICINE, APPLIED STUDIES; RADIOSENSITIVITY; EVALUATION; SKIN; BIOLOGICAL RADIATION EFFECTS; MICE; ANOXIA; RADIOTHERAPY; OXYGEN; BIOLOGICAL EFFECTS; OXYGEN ENHANCEMENT RATIO; GLUTATHIONE; RBE; RADIOSENSITIZERS; LET; TUMOR CELLS; RADIOPROTECTIVE SUBSTANCES

Citation Formats

Stevens, G, Joiner, M, and Joiner, B. Radiosensitization of mouse skin by oxygen and depletion of glutathione. United States: N. p., 1995. Web. doi:10.1016/0360-3016(95)00070-F.
Stevens, G, Joiner, M, & Joiner, B. Radiosensitization of mouse skin by oxygen and depletion of glutathione. United States. https://doi.org/10.1016/0360-3016(95)00070-F
Stevens, G, Joiner, M, and Joiner, B. 1995. "Radiosensitization of mouse skin by oxygen and depletion of glutathione". United States. https://doi.org/10.1016/0360-3016(95)00070-F.
@article{osti_437130,
title = {Radiosensitization of mouse skin by oxygen and depletion of glutathione},
author = {Stevens, G and Joiner, M and Joiner, B},
abstractNote = {To determine the oxygen enhancement ratio (OER) and shape of the oxygen sensitization curve of mouse foot skin, the extent to which glutathione (GSH) depletion radiosensitized skin, and the dependence of such sensitization on the ambient oxygen tension. Carbogen caused the greatest radiosensitization of skin, with a reproducible enhancement of 2.2 relative to the anoxic response. The OER of 2.2 is lower than other reports for mouse skin. This may indicate that the extremes of oxygenation were not produced, although there was no direct evidence for this. Depletion of GSH caused minimal radiosensitization when skin was irradiated under anoxic or well-oxygenated conditions. Radiosensitization by GSH depletion was maximal at intermediate oxygen tensions of 10-21% O{sub 2} in the ambient gas. Increasing the extent of GSH depletion led to increasing radiosensitization, with sensitization enhancement ratios of 1.2 and 1.1, respectively, for extensive and intermediated levels of GSH depletion. In mice exposed to 100% O{sub 2}, a significant component of skin radiosensitivity was due to diffusion of oxygen directly through the skin. Pentobarbitone anesthesia radiosensitized skin in mice exposed to 100% O{sub 2} by a factor of 1.2, but did not further sensitize skin in mice exposed to carbogen. Glutathione levels and the local oxygen tension at the time of irradiation were important determinants of mouse foot skin radiosensitivity. The extent to which GSH levels altered the radiosensitivity of skin was critically dependent on the local oxygen tension. These results have significant implications for potential clinical applications of GSH depletion. 53 refs., 7 figs., 2 tabs.},
doi = {10.1016/0360-3016(95)00070-F},
url = {https://www.osti.gov/biblio/437130}, journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 33,
place = {United States},
year = {Sat Sep 30 00:00:00 EDT 1995},
month = {Sat Sep 30 00:00:00 EDT 1995}
}