Radiosensitization of mouse skin by oxygen and depletion of glutathione

Journal Article · Sat Sep 30 04:00:00 EDT 1995 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/0360-3016(95)00070-F· OSTI ID:437130

Stevens, G; Joiner, M; Joiner, B ^[1]

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1. Gray Lab., Middlesex (United Kingdom); and others

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.

• OSTI ID: 437130
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 2 Vol. 33; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
ANOXIA
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
EVALUATION
GLUTATHIONE
LET
MICE
OXYGEN
OXYGEN ENHANCEMENT RATIO
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY
RADIOSENSITIZERS
RADIOTHERAPY
RBE
SKIN
TUMOR CELLS