pirarubicin and Leukemia-L5178

Aclacinomycin is a member of naturally occurring anthracyclines having three sugar moieties in the molecule. It showed antitumour activity on various mouse and rat tumours. Combination therapy with AraC etc. gave remarkable clinical results on acute myeloid leukaemia. Aclacinomycin strongly inhibits RNA synthesis of the tumour cells. It has lower cardiac toxicity than adriamycin and no mutagenicity. THP-Adriamycin is a derivative of adriamycin designed from the structure of baumycins. It showed stronger effects than adriamycin in inhibiting many mouse tumours such as L1210 and P388 leukaemia, B16 melanoma and colon 38 adenocarcinoma. THP-Adriamycin is rapidly taken up by both adriamycin-sensitive and resistant leukaemic cells. Its level of cardiac toxicity is as low as that of aclacinomycin. Ditrisarubicins are new naturally occurring anthracyclines isolated from Streptomyces having six sugar moieties in the molecule. Ditrisarubicin has a potent cytostatic and antitumour activities on adriamycin resistant mouse leukaemia. Its binding constant to DNA is extremely high compared with other anthracyclines.

Topics: Aclarubicin; Animals; Anthracyclines; Antibiotics, Antineoplastic; Cricetinae; Doxorubicin; Heart; Leukemia L1210; Leukemia L5178; Mice; Myocardium; Naphthacenes; Rats; RNA

Intracellular levels of 4'-O-tetrahydropyranyladriamycin (THP) and adriamycin (ADM) were measured by a fluorospectroscopic method, and the former was shown to be taken up by L5178Y cells much faster than ADM; the uptake velocity of THP at 1 microgram/ml was calculated to be about 170 times faster than that of ADM. High performance liquid chromatography of cell extracts indicated that THP exists mainly in nuclei intact without hydrolysis. The effect of THP in inhibiting [3H]thymidine incorporation into DNA also indicated that THP taken up by cells rapidly went to nuclei and inhibited DNA synthesis. Fifty percent inhibition concentrations of THP or ADM on [3H]-thymidine incorporation during a 60-minute period, 15 minutes after the addition, were 0.1 microgram/ml and 4.2 micrograms/ml, respectively. Similar results were obtained when L1210 cells were used in place of the L5178Y cells.

Topics: Animals; Cell Nucleus; Cells, Cultured; Cytoplasm; DNA, Neoplasm; Doxorubicin; Leukemia L1210; Leukemia L5178; Leukemia, Experimental; Mice; RNA, Neoplasm