[Resistance associated with the glutathione system]

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.