Effects of gemcitabine in normal and transformed human lung cell cultures: cytotoxicity and increase in radiation sensitivity.
OBJECTIVE
Several anticancer drugs increase cell sensitivity to irradiation. Gemcitabine (2', 2' difluorodeoxycytidine) decreases the cellular dNTP pools and thus significantly increases the sensitivity to the DNA damaging effects of low-dose radiation. In this study we have investigated whether gemcitabine may play a role as radiosensitizer also in lung adenocarcinoma treatment.


METHODS
We studied this nucleoside analogue in normal and transformed human cell lines (fetal lung and lung adenocarcinoma). After drug treatment, cell lines were irradiated with different doses. Cell damage following drug treatment and/or irradiation was assessed by measuring intracellular ATP level and by the colony forming assay.


RESULTS
The two cell lines significantly differed in their sensitivity to the toxic effects of the drug; the normal cell line was much more resistant than its transformed counterpart. This difference was observed in both assays, although it was more evident in the colony forming assay. A low radiation dose (50-100 cGy) did not cause any significant damage to transformed cells; normal cells were more resistant and doses up to 500 cGy caused little damage. However, when transformed cells were pretreated for three hours with gemcitabine, even a nontoxic concentration of the drug (1-10 nM) caused a marked sensitization of the cells to irradiation (50-100 cGy). The radiosensitizing effect of gemcitabine could be observed also in normal cells, although these cells were more resistant to the damaging effects of both anticancer treatments.


CONCLUSIONS
This study demonstrates that gemcitabine, a chemotherapeutic agent already used in the clinic, could be proposed as a radiosensitizer for radiation therapy of lung adenocarcinoma, having a clearly potentiating effect on lowdose radiation.
Pacini
S
S
Department of Anatomy, Histology and Forensic Medicine, University of Florence, Policlinico di Careggi, Italy. pacini68@yahoo.com
Milano
F
F
Pinzani
P
P
Pazzagli
M
M
Gulisano
M
M
Ruggiero
M
M
Casamassima
F
F
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000532:radiotherapy*; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D002460:Cell Line; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D014407:Tumor Cells, Cultured; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine