Gemcitabine as a radiosensitizer in undifferentiated tumors

Gemcitabine (dFdC) may cause radiosensitization by specific interference with homologous recombination-mediated DNA double-strand break repair. The radiosensitizing effect of dFdC might be less in normal healthy tissue and more restricted to undifferentiated tumor cells, making it a tumor-selective radiosensitizer. Whether dFdC acts as a radiosensitizer in undifferentiated and well-differentiated rat tumors and on rat foot skin was tested.

Undifferentiated L44 lung tumors in BN rats, MLL prostate tumors in Copenhagen rats, and well-differentiated L42 lung tumors in WAG/Rij rats were used. The tumors were treated with a single X-ray dose, combined or not with dFdC (30 mg/kg) administered 24 h earlier. Tumor volume growth delay was the end-point used. In addition, rat foot skin was treated with a single dose of 22.5 Gy, with or without dFdC. The degree of skin damage was determined according to a scoring system.

For tumor growth delay, the dose-enhancement ratios were 1.37 and 1.23-1.36 for the L44 and MLL tumors, respectively. No radiosensitization was observed for the well-differentiated L42 tumor and foot skin.

Radiosensitization by dFdC was observed in the undifferentiated tumors, but not in the well-differentiated tumor and skin. Our data support further trials to evaluate the usefulness of dFdC as a radiosensitizer in undifferentiated tumors.