An evaluation of the role of glutathione and its associated enzymes in the expression of differential sensitivities to antitumour agents shown by a range of human tumour cell lines.
Glutathione and its associated enzyme activities have been quantitated in a series of human tumour continuous cell lines expressing a range of in vitro sensitivities to certain antitumour agents. Fourteen different parental lines and 15 various drug- and X-ray-selected resistant sublines have been studied. Quantitative relationships between total glutathione levels and related enzyme activities and sensitivities to six clinically-useful antitumour drugs or X-rays, as judged by colony forming assays, have been determined by linear regression analysis. A positive correlation has been identified between glutathione levels and sensitivities to cisplatin. Adriamycin, or to X-rays. In addition, positive correlations were noted between cisplatin sensitivities and glutathione peroxidase and reductase activities and for Adriamycin responses with respect to glutathione peroxidase activity, using cumene hydroperoxide as substrate. However, no positive correlations were noted for glutathione levels or these enzyme activities with differential methotrexate, etoposide, vincristine or 5-fluorouracil cytotoxicities. Furthermore, no direct relationship was apparent between total glutathione S-transferase activities and any of these drug or X-ray sensitivities in this series of cell lines. These data appear to provide further evidence linking altered glutathione metabolism with differential cytotoxicities of certain clinically-useful antitumour agents.
Hosking
L K
LK
Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund, Lincoln's Inn Fields, London, U.K.
Whelan
R D
RD
Shellard
S A
SA
Bedford
P
P
Hill
B T
BT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D005980:Glutathione Reductase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology; D012044:Regression Analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C055423:didimethylsulfoxide dichloroplatinum(II); D004317:Doxorubicin; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione