Gouyette A
CNRS URA 147 (département de pharmacotoxicologie et de pharmacogénétique), institut Gustave-Roussy, Villejuif, France.
Bull Cancer. 1994 Dec;81 Suppl 2:69s-73s.
Several mechanisms of resistance (of bacteria to antibiotics, of plants to herbicides, of insects to insecticides, of cancer cells to cytotoxic agents...) have now been described. The most studied one is the glycoprotein coded by the mdr1 gene, which is involved in the efflux of numerous compounds of natural origin (anthracyclines, podophyllotoxins...) thus decreasing the intracellular concentration of such drugs. Nevertheless, many chemotherapeutic protocols include alkylating agents, such as cyclophosphamide and cisplatin, which are electrophilic species prone to react readily with the tripeptide glutathione, most often through glutathione-S-transferases. Therefore, it appears of major importance to evaluate the role of glutathione and that of the polymorphism of the glutathione-S-transferases, as prognostic factors in the response to chemotherapy.
目前已描述了几种耐药机制(细菌对抗生素、植物对除草剂、昆虫对杀虫剂、癌细胞对细胞毒性药物……的耐药机制)。研究最多的是由mdr1基因编码的糖蛋白,它参与多种天然来源化合物(蒽环类抗生素、鬼臼毒素……)的外排,从而降低此类药物的细胞内浓度。然而,许多化疗方案中都包含烷化剂,如环磷酰胺和顺铂,它们是亲电物质,很容易与三肽谷胱甘肽反应,最常见的是通过谷胱甘肽-S-转移酶。因此,评估谷胱甘肽的作用以及谷胱甘肽-S-转移酶多态性作为化疗反应预后因素的作用显得至关重要。