Cholon A, Giaccia A J, Lewis A D, Hickson I, Brown J M
Department of Radiation Oncology, Stanford University, CA 94305.
Int J Radiat Oncol Biol Phys. 1992;22(4):759-63. doi: 10.1016/0360-3016(92)90519-n.
The glutathione S-transferases (GST's) are cytosolic dimeric proteins that are composed of three family members, alpha, pi, and mu, and a fourth microsomal member. These four family members are primarily involved in cellular detoxification of xenobiotics and hydroperoxides. Recently, a strong correlation has been found between the overexpression of GST's and resistance to chemotherapeutic drugs. In comparison to chemotherapy, little is known about the role of GST's in the cellular response to ionizing radiation. To determine which GST's may be involved in this response, we have identified Chinese hamster ovary cell lines that possess different levels of alpha and pi GST isozyme activity. The survival of these cell lines to ionizing radiation was similar to that of wild-type Chinese hamster ovary-KI cells from which they were derived. Although differences in GST levels did not affect ionizing radiation sensitivity per se, we found that ionizing radiation decreased the amount of cytosolic pi GST without affecting alpha GST levels. Taken together, these data suggest that GST's are involved in the cellular response against oxidative stress generated by ionizing radiation.
谷胱甘肽S-转移酶(GST)是胞质二聚体蛋白,由α、π和μ三个家族成员以及第四个微粒体成员组成。这四个家族成员主要参与外源性物质和氢过氧化物的细胞解毒过程。最近,人们发现GST的过表达与对化疗药物的耐药性之间存在密切关联。与化疗相比,关于GST在细胞对电离辐射反应中的作用知之甚少。为了确定哪些GST可能参与这一反应,我们鉴定了具有不同水平α和πGST同工酶活性的中国仓鼠卵巢细胞系。这些细胞系对电离辐射的存活率与它们所源自的野生型中国仓鼠卵巢-KI细胞相似。虽然GST水平的差异本身并不影响对电离辐射的敏感性,但我们发现电离辐射会降低胞质πGST的量,而不影响αGST的水平。综上所述,这些数据表明GST参与了细胞对电离辐射产生的氧化应激的反应。