A Radioprotective Effect of Imatinib (Gleevec^®) in Human Squamous Carcinoma Cells.

Bartkowiak, Detlef; Hipp, Peter; Mendonca, Marc; Röttinger, Erwin

To study the radiation response-modifying effect of imatinib (Gleevec®) in a squamous cell carcinoma line, PECA. 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. Inactivating 50% of the PECA cells required approximately 7 μM 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. 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.

IMATINIB; RADIATION; SQUAMOUS cell carcinoma; DRUG resistance; BIOCHEMICAL genetics; IMMUNOHISTOCHEMISTRY

Strahlentherapie und Onkologie, 2007, Vol 183, Issue 8, p432

0179-7158

Academic Journal

10.1007/s00066-007-1680-7