Table 3.

Enhancement of the Efficacy of Cisplatin, Temozolomide, and BCNU against Melanoma Tumor Cell Lines with MDS

Cell lineO6-benzylguanine/MDS+Cisplatin*+Temozolomide*+BCNU*
Treatment 1 (O6-benzylguanine 24 h, MDS 96 h, chemotherapy, methionine 2 wk)
    MEWO10.18 ± 0.30.105 ± 0.0730.07 ± 0.04
    M10310.05 ± 0.020.012 ± 0.004Eradicated
    WM3510.08 ± 0.020.025 ± 0.012Eradicated
    E.DERM10.64 ± 0.130.87 ± 0.120.55 ± 0.08
Treatment 2 (O6-benzylguanine 24 h, MDS 96 h, methionine 24 h, chemotherapy, methionine 2 wk)
    MEWO10.27 ± 0.60.15 ± 0.050.13 ± 0.06
    M10310.12 ± 0.040.032 ± 0.010.03 ± 0.02
    WM3510.13 ± 0.040.033 ± 0.010.04 ± 0.01
    E.DERM10.72 ± 0.140.89 ± 0.090.67 ± 0.12
  • NOTE: MEWO, M103, WM35, and E.DERM were treated with O6-benzylguanine (30 μmol/L) for 24 hours followed by MDS alone for an additional 96 hours. When multinucleated cells were fully arrested, they were treated with cisplatin (30 μmol/L), temozolomide (200 μmol/L), or BCNU (30 μmol/L) and placed in methionine medium, and their ability to grow was tested using a clonogenic assay (Materials and Methods). Colonies of ≥50 cells were counted and expressed as fraction of control (no cytotoxic drug). Mean ± SD of three determinations.

  • * Concentrations of the drugs used did not have a significant effect on the survival and proliferation of cells growing in methionine-efficient medium as determined by clonogenic assays.

  • Fraction of surviving cells compared with their respective controls. These fractions were determined by counting the number of colonies in agar after 2 weeks of growth and comparing such numbers to controls (no cytotoxic agent).