Radiosensitization of human solid tumor cell lines with gemcitabine.
Gemcitabine has high clinical activity in several solid tumors that are treated with radiotherapy and/or chemotherapy. The mode of action of gemcitabine involves a number of intracellular changes that are shared by other radiation sensitizing anticancer drugs. There is therefore a clear rationale for investigating the interaction between gemcitabine and radiation in human cancer cell lines in vitro. Gemcitabine has been shown to be a potent radiosensitizer in human colorectal, pancreatic, and other solid tumor cell lines. Gemcitabine produces radiation enhancement ratios that are higher than those of other established radio-sensitizing agents, and this radiation enhancement occurs at low noncytotoxic concentrations. Radiosensitization increases with dose and with duration of exposure to gemcitabine, and is greatest when exposure to gemcitabine precedes radiation. The primary radiosensitizing effect of gemcitabine seems to be associated with depletion of endogenous nucleotide pools; deoxyadenosine triphosphate reduction is particularly striking, even at the lowest concentrations of gemcitabine. These studies suggest a number of approaches that are relevant to the clinical use of gemcitabine in patients with solid tumors.
Shewach
D S
DS
Departments of Pharmacology and Radiation Oncology, University of Michigan Medical Center, Ann Arbor 48109-0504, USA.
Lawrence
T S
TS
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine