Gemcitabine as a radiosensitizer in undifferentiated tumors.
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.


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.


CONCLUSIONS
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.
Kal
Henk B
HB
Department of Radiation Oncology, University Medical Center, Post Box 85500, 3508 GA Utrecht, The Netherlands. H.B.Kal@UMCUtrecht.nl
El Sharouni
Sherif Y
SY
Barten-van Rijbroek
Angeliqué D
AD
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D008297:Male; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D012867:Skin / Q000528:radiation effects; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine