The importance of peroxide and superoxide in the X-ray response.
Radiation produces a number of damaging radicals as well as peroxide. The chief cellular protection against these radicals, their secondary reactants and peroxide is the cellular glutathione (GSH), GSH peroxidase, GSH-S-transferase (GSHTase), and catalase enzymes. Inhibition of cellular catalase alone does not enhance the aerobic radiation response because cellular GSH peroxidase is equally effective in reducing peroxide. However, inhibition of GSHTase, and partial inhibition of peroxidase by L-buthionine sulfoximine (LBSO)-linked GSH depletion, results in an increased aerobic radiation response. The major pathway for peroxide reduction is the GSH peroxidase. The enzyme is accountable for 70% inactivation of low peroxide concentrations. Catalase accounts for the remaining inactivation. However, it is difficult to assess the relative contributions of GSHTase and peroxidase to the inactivation of radiation-produced hydroperoxides. Our data suggest that GSH depletion results in the inhibition of cellular GSHTase before it inhibits GSH peroxidase. Therefore, part of the increased aerobic radiation response maybe due to cellular inability to reduce hydroperoxides. Peroxide is not a substrate for GSHTase. However, total inhibition of peroxidase by L-BSO plus N-ethylmaleimide (NEM) treatment maximizes the aerobic radiation response. Total inhibition of GSH-S-transferase and peroxidase would block both peroxide and hydroperoxide reduction.
Biaglow
J E
JE
Dept. of Radiation Oncology, University of Pennsylvania, Phil. 19104.
Mitchell
J B
JB
Held
K
K
D002374:Catalase / Q000502:physiology; D002470:Cell Survival / Q000528:radiation effects*; D005978:Glutathione / Q000502:physiology; D005979:Glutathione Peroxidase / Q000502:physiology; D005982:Glutathione Transferase / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010545:Peroxides; D013481:Superoxides; D014407:Tumor Cells, Cultured
D010545:Peroxides; D013481:Superoxides; D002374:Catalase; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D005978:Glutathione