Effects of azetidine-2-carboxylic acid on treatments of hepatoma cells with single or fractionated X-ray irradiations and on thermal radiosensitization in normal and thermotolerant cells.
The amino acid analog azetidine-2-carboxylic acid (azetidine) is a potent sensitizer to both hyperthermia and ionizing radiation. Incubation of H35 hepatoma cells with 2.5 mM azetidine before or after treatments with X-rays causes a time- and sequence-dependent enhancement of cell killing. Exposure of cells to 1-1.5 mM azetidine for 96 h in combination with repeated doses of 3 Gy X-rays at 24 h intervals causes an enhanced reduction of the surviving cell population due to both radiosensitization and an additional growth inhibition. Azetidine does not prevent the induction of thermotolerance after a heat shock. This thermotolerance proportionally reduces thermal radiosensitization but does not seem to affect azetidine radiosensitization. It is suggested that thermal radiosensitization and azetidine radiosensitization operate by different mechanisms.
van Rijn
J
J
Department of Radiation Oncology, Academic Hospital Vrije Universiteit, Amsterdam, The Netherlands. j.vanrijn.radiobiol@med.vu.nl
van den Berg
J
J
van der Mast
C A
CA
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001383:Azetidinecarboxylic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D016923:Cell Death; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D018869:Heat-Shock Response / Q000187:drug effects; D006979:Hyperthermia, Induced; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011879:Radiotherapy Dosage; D051381:Rats; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D001383:Azetidinecarboxylic Acid