Radiosensitization of human T-cell leukemia by thymidine and 41.8 degrees C hyperthermia in vitro.
This study tested whether thymidine, a naturally occurring nucleoside metabolite, could increase the sensitivity of human T-cell neoplasms to ionizing irradiation and whether adding 41.8 degrees C hyperthermia (X 1 h) to the combination of thymidine and irradiation would further enhance killing of cells by radiation. The magnitude of cytotoxicity induced directly by thymidine was also evaluated. Finally, the ability of 2'-deoxycytidine to prevent thymidine-induced cytotoxicity and radiosensitization was studied. Using JM and MOLT3, two human T-cell acute lymphoblastic leukemias, it was found that thymidine itself was cytotoxic and the toxicity appeared rapidly upon exposure to the drug (i.e., at 4 h). Thymidine caused significant radiosensitization, and thymidine plus 1 h of 41.8 degrees C hyperthermia enhanced radiation-induced killing significantly more than did thymidine or hyperthermia separately. The addition of 2'-deoxycytidine only partly reversed thymidine-induced killing and did not prevent thymidine-induced radiosensitization. The applicability of these results to the clinical management of T- and null-cell malignancies is discussed, as is the presumed mechanistic basis for these observations relative to deoxyribonucleoside metabolism, NAD metabolism, and inhibition of poly(ADP-ribose) polymerase.
Cohen
J D
JD
Department of Neurological Surgery, University of Wisconsin Clinical Sciences Center, Madison 53792.
Schmitt
C L
CL
Robins
H I
HI
D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D006979:Hyperthermia, Induced; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000628:therapy*; D011836:Radiation Tolerance / Q000187:drug effects* / Q000502:physiology; D013936:Thymidine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects
D002588:Cesium Radioisotopes; D003841:Deoxycytidine; D013936:Thymidine