Unlabelled iododeoxyuridine increases the cytotoxicity and incorporation of [1251]-iododeoxyuridine in two human glioblastoma cell lines.
Iododeoxyuridine (IUdR), labelled with radioiodines emitting Auger, alpha or beta- radiation, has been proposed as a therapeutic tool in the treatment of cancer. However, the low per cent incorporation in tumour cells and limited cytotoxicity are major obstacles for such an application. Using unlabelled IUdR as a modulator, we have studied the in vitro cytotoxicity of [125I]-IUdR in two human glioblastoma cell lines. Surprisingly, an enhanced cytotoxicity of [125I]-IUdR was observed in the presence of 0.3-10 microM concentrations of unlabelled IUdR in U251 glioblastoma cells and to a lesser extent in LN229 cells. The presence of unlabelled IUdR unexpectedly increased the incorporation of [125I]-IUdR in both cell lines. Thymidine competitively blocked the cytotoxic effects of combined unlabelled and [125I]-labelled IUdR in these cells and DNA-incorporation of radiolabelled IUdR.
Xiao
W H
WH
Division of Nuclear Medicine, University Hospital of Geneva, Switzerland.
Dupertuis
Y M
YM
Mermillod
B
B
Sun
L Q
LQ
de Tribolet
N
N
Buchegger
F
F
D001667:Binding, Competitive; D002470:Cell Survival / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007065:Idoxuridine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D007065:Idoxuridine