Interactions of thymidine, hyperthermia, and cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) in human T-cell leukemia.
Using JM and MOLT3, two human T-cell acute lymphoblastic leukemia cell lines, we investigated the ability of 24-h thymidine exposures to enhance the cytotoxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin). Clinically achievable thymidine concentrations (for 24 h) significantly enhanced carboplatin killing. Unexpectedly, thymidine-carboplatin enhancement was as great at a relatively low 200-micrograms thymidine/ml as at the clinically much more toxic range of 1000 micrograms/ml. For a constant thymidine concentration (500 micrograms/ml), thymidine-carboplatin interaction increased with longer thymidine exposures until about 16 to 24 h. Thymidine and 41.8 degrees C hyperthermia (for 1 h) together enhanced carboplatin killing significantly more than did hyperthermia-carboplatin or thymidine-carboplatin combinations. These results show that relatively brief, presumptively nonmyelosuppressive thymidine exposures can significantly increase carboplatin killing. Carboplatin-thymidine killing can then be further augmented by 41.8 degrees C hyperthermia.
Cohen
J D
JD
University of Wisconsin Clinical Cancer Center, Madison 53792.
Robins
H I
HI
Schmitt
C L
CL
Tanner
M A
MA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D004357:Drug Synergism; D006321:Heart; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D013936:Thymidine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin; D013936:Thymidine