Gemcitabine as a Radiosensitizer in Undifferentiated Tumors

• Published in: Anticancer research Vol. 26; no. 1A; pp. 139 - 145
• Main Authors: KAL, Henk B, EL SHAROUNI, Sherif Y, BARTEN-VAN RIJBROEK, Angeliqué D
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.01.2006
• Subjects: Animals; Antimetabolites, Antineoplastic - pharmacology; Biological and medical sciences; Carcinoma - drug therapy; Carcinoma - radiotherapy; Combined Modality Therapy; Deoxycytidine - analogs & derivatives; Deoxycytidine - pharmacology; Dose-Response Relationship, Radiation; Female; Lung Neoplasms - drug therapy; Lung Neoplasms - radiotherapy; Male; Medical sciences; Radiation-Sensitizing Agents - pharmacology; Rats; Rats, Inbred BN; Skin - radiation effects; Tumors; Antineoplastic agent; undifferentiated tumors; Cancerology; Radiosensitizing agent; Antimetabolic; Gemcitabine; Pyrimidine derivatives; Fluorine Organic compounds; radiosensitizer; Pyrimidine nucleoside; Undifferentiated tumor
• ISSN: 0250-7005; 1791-7530

Background: 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. Materials and Methods: 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. Results: 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. Conclusion: 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.