Circumvention of drug resistance of P388/R cells by the combination of adriamycin and mitoxantrone with hyperthermia (42 degrees C).
P388/R, the adriamycin (ADR) resistant subline of murine P388 lymphocytic leukemia was cross-resistant to the drug mitoxantrone (MTN). One hour hyperthermia at 42 degrees C (HT) was employed along with ADR (10 micrograms/ml) and MTN (10 micrograms/ml) for circumventing the drug resistance of P388/R cells in in vitro-in vivo bioassays. Inhibition in the incorporation of tritiated thymidine into cellular DNA was measured to check the in vitro cytotoxic effect. Hyperthermia, ADR and MTN alone could not bring about significant degree of inhibition of DNA biosynthesis whereas the combination of ADR and MTN along with HT resulted in a synergistic cytotoxic action (p less than 0.001 and 0.01, respectively). The cells were treated with the drugs in vitro and inoculated into BDF1 mice. It was observed that ADR, MTN or HT pretreatment of the cells resulted in an increase of the life-span of the mice by 4.0-25.0%, 10-20% and 44-50%, respectively, whereas the pretreatment of cells with the combination of ADR and MTN with HT resulted in an increase by 104-125% and 212-220% in life-span of the mice, respectively. Studies revealed that the combination ADR-HT and MTN-HT resulted in circumvention of resistance of P388/R cells to ADR and MTN.
Juvekar
A S
AS
Cellular Chemotherapy Unit, Tata Memorial Center, Parel, Bombay, India.
Chitnis
M P
MP
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage; D004351:Drug Resistance / Q000235:genetics; D006979:Hyperthermia, Induced; D007941:Leukemia P388 / Q000235:genetics / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008942:Mitoxantrone / Q000008:administration & dosage; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004317:Doxorubicin; D008942:Mitoxantrone; D013936:Thymidine