Biaglow J E, Varnes M E, Epp E R, Clark E P, Tuttle S W, Held K D
Department of Radiation Oncology, University of Pennsylvania, Philadelphia 19104.
Int J Radiat Oncol Biol Phys. 1989 May;16(5):1311-4. doi: 10.1016/0360-3016(89)90305-2.
We will review the relationships between glutathione (GSH), protein thiols, and cellular responses to radiation, peroxides, and peroxide-producing drugs. Our primary interest involves the behavior of sulfhydryls as electron and hydrogen carriers, and their capacity to protect various target molecules against radiation and peroxidative damage. We used reagents such as L-buthionine sulfoximine (LBSO), alone and in combination with N-ethyl maleimide (NEM), diamide, and dimethylfumarate, to decrease GSH so that it could no longer participate in the electron transfer reactions. Our results indicate that aerobic sensitization produced by GSH depletion can be further enhanced if electron-accepting agents, such as tertiary butyl hydroperoxide (t-BOOH), are present during irradiation. Hydroperoxide is a substrate for glutathione peroxidase and diverts electrons and hydrogen away from target molecules during its reduction. Sensitivity to radiation seems to be due to the inhibition of the mitochondria's capacity to reduce hydroperoxide. We will also report the mitochondria's ability to reduce the oxygen radicals produced by radiation and drugs. Data also indicate that t-BOOH oxidizes protein thiols which are enzymatically involved in repair of DNA damage.
我们将综述谷胱甘肽（GSH）、蛋白质硫醇与细胞对辐射、过氧化物及产过氧化物药物的反应之间的关系。我们主要关注巯基作为电子和氢载体的行为，以及它们保护各种靶分子免受辐射和过氧化损伤的能力。我们使用了诸如L-丁硫氨酸亚砜胺（LBSO）等试剂，单独使用或与N-乙基马来酰亚胺（NEM）、二酰胺和富马酸二甲酯联合使用，以降低GSH，使其不再参与电子转移反应。我们的结果表明，如果在照射期间存在电子接受剂，如叔丁基过氧化氢（t-BOOH），GSH耗竭产生的需氧增敏作用可进一步增强。过氧化氢是谷胱甘肽过氧化物酶的底物，在其还原过程中会使电子和氢从靶分子转移开。对辐射的敏感性似乎是由于线粒体还原过氧化氢的能力受到抑制。我们还将报告线粒体还原由辐射和药物产生的氧自由基的能力。数据还表明，t-BOOH会氧化参与DNA损伤修复的蛋白质硫醇。
