title: Role of glutathione peroxidase in the radiation response of mouse kidney.
abstract: 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.
authors.affiliation: Gray Laboratory of the Cancer Research Campaign, Mount Vernon Hospital, Northwood, Middlesex, U.K.
authors.forename: G N
authors.initials: GN
authors.lastname: Stevens
authors.forename: M C
authors.initials: MC
authors.lastname: Joiner
authors.forename: B
authors.initials: B
authors.lastname: Joiner
authors.forename: H
authors.initials: H
authors.lastname: Johns
authors.forename: M R
authors.initials: MR
authors.lastname: Stratford
mesh_terms: 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
chemical_list: D005979:Glutathione Peroxidase; D012643:Selenium