Dexrazoxane has no impact on sensitivity of childhood leukemic blasts to daunorubicin.
Dexrazoxane (DEX) prevents the formation of free radical, lipid peroxidation and cardiotoxicity caused by anthracyclines. Due to a concern about its possible interference with anthracyclin cytotoxicity, the in vitro effect of DEX on daunorubicin (DNR) cytotoxicity, cell cycle and induction of apoptosis by annexin-V was investigated. The sensitivity to DEX, DNR and their combination was tested by the MTT assay in human promyelocytic leukemia HL-60, the erythroid blast crisis CML K562 cell lines and in 45 children with ALL and AML. Cell cycle analysis and annexin-V expression were performed by flow cytometry. It has been observed that DEX itself weakly, but significantly caused cytotoxicity in both cell lines and in patient samples, especially in initial ALL samples. DEX sensitized K562 and HL60, but not patient samples, to cytotoxicity of DNR. The percentage of necrotic/apoptotic cells, as detected in cell cycle analysis and annexin V staining, was higher after exposure to DEX +/- DNR, when compared to respective samples not treated with DEX, in both cell lines but not in patient samples. Expression of annexin V induced by DEX in both cell lines was enlarged, regardless of the presence of DNR. This difference was not observed in patient samples, however, the number of cells expressing annexin V was higher after exposure to DEX +/- DNR in comparison to respective samples not treated with DEX. In conclusion, it seems that DEX possibly has no impact on the sensitivity of childhood leukemic blasts to DNR, however, has weak cytotoxic properties itself.
Styczynski
J
J
Department of Pediatric Hematology and Oncology, Medical University, ul. Gersona 17-8, 85-305 Bydgoszcz, Poland.
Wysocki
M
M
Balwierz
W
W
Kowalczyk
J R
JR
D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003630:Daunorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D007223:Infant; D020014:K562 Cells; D007938:Leukemia / Q000473:pathology*; D011929:Razoxane / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D011929:Razoxane; D003630:Daunorubicin