POTENTIATION OF DNA-REACTIVE ANTI-NEOPLASTIC AGENTS AND PROTECTION AGAINST S-PHASE-SPECIFIC AGENTS BY ANGUIDINE IN CHINESE-HAMSTER OVARY CELLS

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (7) , 3070-3073
Abstract
Anguidine, a protein synthesis inhibitor, induces a reversible cell cycle arrest in exponentially growing Chinese hamster overy cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia and radiation was investigated. Anguidine greatly potentiated the cytotoxic activity of cis-dichlorodiammineplatinum(II) and melphalan by abolishing the initial shoulder and steepening the subsequent exponential portion of the survival curves. Bleomycin-induced cell kill was also potentiated by anguidine pretreatment but to a lesser extent. However, anguidine pretreatment did not substantially alter radiation cytotoxicity. In contrast, anguidine markedly reduced the lethal effect of hydroxyurea, 5-fluorouracil and hyperthermia, 3 modalities with S-phase activity. To investigate whether both anguidine-induced potentiation and protection of cells by different antitumor agents were due to its induction of complete suspension of cycle traverse, experiments were also conducted with plateau-phase cultures. Whereas anguidine potentiated cis-dichlorodiammineplatinum(II) cytotoxicity in an identical fashion as noted in exponentially growing cells, its protective effect against lethal damage from Adriamycin was absent. Thus, it appears that the 2 opposite effects of anguidine modification of cell kill by cytotoxic agents (protection and potentiation) come about by 2 different mechanisms, with cell cycle arrest underlying cytoprotection and the mechanism of synergistic toxicity remaining obscure.