A radioprotective effect of imatinib (Gleevec) in human squamous carcinoma cells.
OBJECTIVE
To study the radiation response-modifying effect of imatinib (Gleevec) in a squamous cell carcinoma line, PECA.


METHODS
Cytotoxicity was determined by colony forming and multiplying capacity. Drug stability was shown by HPLC. Multidrug resistance phenotype was studied by rhodamine-123 efflux. Cell-cycle responses were measured by flow cytometry. Homologous recombination repair was determined by Rad51 immunohistochemistry.


RESULTS
Inactivating 50% of the PECA cells required approximately 7 microM imatinib. The drug did not decay nor was it degraded during test periods. Drug efflux occurred only to a minor extent. Multiplying capacity but not survival fractions revealed a radioprotective effect of imatinib. There were only minor cell-cycle alterations in the presence of imatinib but the rate of Rad51-positive repair foci was significantly increased.


CONCLUSIONS
PECA cells apparently lack a highly specific target for imatinib. In cells surviving at high drug concentrations, imatinib may exert a radioprotective effect on multiplying capacity by inducing DNA repair. Under prolonged exposure, drug-resistant cells may show an accelerated recovery from acute or delayed radiation damage.
Department of Radiooncology, University Hospital Ulm, Ulm, Germany. detlef.bartkowiak@uniklinik-ulm.de
Detlef
D
Bartkowiak
Peter R
PR
Hipp
Marc S
MS
Mendonca
Erwin M
EM
Röttinger
D000970:Antineoplastic Agents / Q000008:administration & dosage; D001549:Benzamides; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D011836:Radiation Tolerance / Q000187:drug effects*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D011837:Radiation-Protective Agents; D000068877:Imatinib Mesylate