carubicin and valrubicin

Topics: Aclarubicin; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Carubicin; Daunorubicin; Doxorubicin; Female; Glycosides; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphoma; Naphthacenes; Ovarian Neoplasms; Sarcoma

Leukemia cells from 4 acute myelocytic leukemia (AML) and 1 acute lymphocytic leukemia (ALL) patients were incubated with a set of 6 anthracycline agents: Adriamycin (Am), 4'-epi-Adriamycin (4'-epi-Am), daunorubicin (Dm), 4-demethoxy-daunorubicin (4-dDm), carminomycin (Cm) and N-trifluoroacetyl-Am-14-valerate (AD32). Cells were assayed for drug uptake after incubation for 2 h, and for DNA damage and drug retention 4 h later. Uptake and retention patterns were characteristic for each agent and fairly uniform for the different cell populations. In contrast, profiles of the amount of DNA damage produced reflected striking differences in each population of cells. These individual responses raise the possibility that leukemic cells resistant to one anthracycline may yet be sensitive to another.

Topics: Carubicin; Cells, Cultured; Daunorubicin; DNA Repair; DNA, Neoplasm; Doxorubicin; Drug Evaluation; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Prognosis

We have used a laser flow cytometer to excite and quantitate the intracellular fluorescence of cells exposed in vitro and in vivo to various anthracyclines. In cells exposed to Adriamycin (ADR), intracellular drug fluorescence appeared slowly and reached a peak after 4 hr of incubation. Cells incubated with 10 micrograms/ml were 5 times more fluorescent than were cells incubated with 1 microgram/ml. Cells exposed to daunomycin were 2 to 4 times more fluorescent than were cells similarly exposed to ADR, and the intracellular appearance of daunomycin fluorescence was much more rapid. Cells exposed to N-trifluoroacetyladriamycin and carminomycin had higher amounts of intracellular fluorescence (2 to 4 times), and peak values were reached much more rapidly than in cells exposed to ADR. In cells exposed to rubidazone, fluorescence increased 2- to 4-fold with increased drug concentration and length of exposure. In contrast, nogalamycin fluorescence reached a peak after 60 min of incubation, and a 10-fold increase in drug concentration increased fluorescence only 2-fold. In animals given injections of ADR (4 mg/kg) and sacrificed after 3 hr, drug fluorescence could be detected in tumor and spleen cells. In contrast, fluorescence in heart nuclei was barely recognizable. However, incubation of isolated nuclei in ADR (1 microgram/ml) showed that bone marrow and heart nuclei had greater amounts of ADR fluorescence (2- to 3-fold) than did spleen or liver nuclei similarly treated. The use of laser flow cytometry for monitoring intracellular anthracycline transport, binding, and efflux is demonstrated.

Topics: Antibiotics, Antineoplastic; Carubicin; Cell Nucleus; Cells, Cultured; Cytoplasm; Daunorubicin; Doxorubicin; Glycosides; Humans; Lasers; Microscopy, Fluorescence; Naphthacenes; Nogalamycin; Spectrometry, Fluorescence

The kinetics of cellular and nuclear incorporation of a number of new anthracyclines into daunorubicin-sensitive and -resistant Ehrlich ascites cells were determined in vitro. For comparative quantitative analyses the substances were extracted with a 0.3 N HCl/50% ethanol (v/v) solution from either whole cells or purified citric acid nuclei after various intervals of in vitro incubation. At steady state the intracellular and intranuclear concentrations of daunorubicin and doxorubicin were reduced by about 50% in the resistant cell line. Marcellomycin and carminomycin concentrations were only reduced by 9% and 11%, respectively, and no differences between sensitive and resistant cells were seen in the case of aclacinomycin A and AD 32. When the ratios of nuclear to cellular drug were determined at steady state lowest value was found for AD 32 (0.26). In contrast, aclacinomycin A and carminomycin were mainly (78% and 74%) and marcellomycin almost exclusively (95%) concentrated in the nucleus. When the total amounts of drug incorporated per cell were compared, the highest values were measured for aclacinomycin A and the lowest for AD 32 both in the sensitive and the resistant tumor. Additional determinations of the 50% inhibitory concentrations for thymidine uptake showed similar differences between these anthracyclines which were not related to the potency of the drugs in vivo. It is concluded that apart from nuclear incorporation and inhibition of DNA synthesis other factors may be decisive for anthracycline-induced cytotoxicity.

Topics: Aclarubicin; Animals; Anthracyclines; Antibiotics, Antineoplastic; Carcinoma, Ehrlich Tumor; Carubicin; Cell Nucleus; Daunorubicin; DNA, Neoplasm; Doxorubicin; Drug Resistance; Female; In Vitro Techniques; Mice; Naphthacenes