[Biochemical mechanisms of resistance to a new antineoplastic agent amin(cyclopeptidylamin)-S-(-)-malatoplatinum (II) (cycloplatam)].
The "in vivo" effect of cycloplatam on DNA synthesis in leukemia P388/o (parent strain), P388/c (cycloplatam-resistant strain) and in some organs of tumour-bearing mice, such as spleen, kidney, gastrointestinal mucosa (GI mucosa) and bone marrow, has been studied. Cycloplatam induced a deep and stable inhibition of DNA synthesis in leukemia cells and kidney. DNA synthesis in normal dividing cells (GI mucosa, bone marrow, spleen) was shown to recover more rapidly than in leukemia cells and kidney after cycloplatam treatment. The GSH level was increased tenfold in leukemia P388/c cells in comparison with P388/o. The glutathione peroxidase and glutathione reductase activities were increased twofold in the resistant strain in comparison with the parent strain, while the activity of glutathione-S-transferase showed a 1.5-fold increase. Administration of cycloplatam to tumour-bearing mice caused a marked increase of the GSH level in the both leukemia strains. Alterations in GSH-dependent enzymes following cycloplatam therapy were expressed in a lesser degree. These data indicate that GSH and GSH-dependent enzymes may play an important role in the resistance of P388 leukemia cells to cycloplatam.
Dederer
L Iu
LIu
Lankin
V Z
VZ
Konovalova
A L
AL
Gorbacheva
L B
LB
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004351:Drug Resistance; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007941:Leukemia P388 / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009944:Organoplatinum Compounds / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C055928:cycloplatam; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione
Issledovaniia biokhimicheskikh mekhanizmov rezistentnosti k novomu protivoopukholevomu preparatu amin(tsiklopentilamin)-S-(-)-malatoplatine (II) (tsikloplatamu).