Role of glutathione peroxidase in the radiation response of mouse kidney.
Glutathione peroxidase (GSH-Px) has been implicated in mediating the radioprotective effects of glutathione (GSH). This hypothesis was tested in vivo by determining the effect of GSH-Px depletion on the radiation response of murine kidneys. Renal GSH-Px levels were depleted to 17% of control values by feeding animals a selenium deficient diet for 6 weeks; this had no significant effect on renal levels of GSH or GSH-S-transferase (GST). However, we also tested the effect of direct depletion of GSH to 3-4% of control values, using a combination of DL-buthionine sulphoximine (BSO) and diethyl maleate (DEM). Kidneys with normal or depleted levels of GSH-Px and/or GSH were irradiated with 240kVp X rays (2 fractions, 7 days apart to minimize intestinal injury). Mice breathed 7% oxygen during irradiation. Renal damage was assessed at 20, 25, and 32 weeks after the first fraction of X rays, in terms of reduced hematocrit and renal clearance of 51Cr-EDTA. Depletion of GSH-Px levels to 17% of control did not alter renal radiosensitivity, but depletion of GSH to 3-4% of control values radiosensitized the kidney by a factor of 1.4. Depletion of both GSH and GSH-Px together did not radiosensitize the kidney any more than was achieved by GSH depletion alone.
Stevens
G N
GN
Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, Northwood, Middlesex, U.K.
Joiner
M C
MC
Joiner
B
B
Johns
H
H
Stratford
M R
MR
D000818:Animals; D004032:Diet; D005260:Female; D005979:Glutathione Peroxidase / Q000502:physiology*; D007668:Kidney / Q000528:radiation effects*; D051379:Mice; D008808:Mice, Inbred CBA; D011836:Radiation Tolerance; D012643:Selenium / Q000172:deficiency
D005979:Glutathione Peroxidase; D012643:Selenium