RESUMEN
Two strains of P388 murine leukemia with acquired resistance to rubomycin (P388/rm) and its nitroxyl derivative ruboxyl (P388/rx). The rubomycin resistance has been developed by the 14th generation and ruboxyl one-by the 8th generation. The growth kinetic patterns and the cell cycle time of the parent and resistant strains were similar. An increased tumourogenicity of both resistant strains cells was found. The resistance development was accompanied by the appearance of the additional chromosome materials, namely of homogeneously staining region (P388/rx) and of double chromatin bodies (P388/rm). The partial recovery of sensitivity to rubomycin occurred during 36 generations (1 year). Simultaneously the genetic markers have been lost. The recovery of sensitivity to ruboxyl in this period was not observed. The obtained resistant strains possessed the multidrug resistance: the cross resistance of P388/rm and P388/rx to actinomycin D, Vinca alkaloids and colchicine was shown.
Asunto(s)
Daunorrubicina/análogos & derivados , Daunorrubicina/uso terapéutico , Leucemia P388/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Animales , Resistencia a Medicamentos , Leucemia P388/genética , RatonesRESUMEN
L 1210 leukemia strain resistant to diazan (L 1210/D1) was studied for its drug sensitivity in comparison with the parent strain. The resistant strain exhibited significantly higher sensitivity to nine drugs: dopan, sarcolysine, apirazidin, cyclophosphane, 6-mercaptopurine, thiophosphamide, rubomycin, vinblastine and vincristine. L 1210/D1 gained cross resistance to four drugs: 1-(2-chloroethyl)-3-(2, 6-dioxy-3-piperidyl)-1-nitrosourea, methotrexate, 5-fluorouracil and ftorafur. The resistant strain sensitivity remained unchanged (in comparison with the parent strain) to seven drugs: degranol, prospidin, nitrosomethylurea, chlorozotocin, deazauridine, bleomycin and L-asparaginase (crasnitine).
Asunto(s)
Antineoplásicos/antagonistas & inhibidores , Compuestos de Diazonio/antagonistas & inhibidores , Leucemia L1210/tratamiento farmacológico , Animales , Evaluación Preclínica de Medicamentos , Resistencia a Medicamentos , RatonesRESUMEN
Diazane inhibited for 25 hours the division of cells being at S-phase during its administration. The renewal of cell division was followed by their selective death. The substance failed to affect cells being at G2-phase of at termination of S-phase during its administration.
Asunto(s)
Compuestos Azo/farmacología , Ciclo Celular/efectos de los fármacos , Compuestos de Diazonio , Leucemia L1210/tratamiento farmacológico , Mitosis/efectos de los fármacos , Succinatos/farmacología , Animales , ADN de Neoplasias/biosíntesis , Depresión Química , Leucemia L1210/metabolismo , RatonesRESUMEN
The growth of the Harding--Passey murine melanoma has been studied. The time of the tumor size doubling was found equal to 29, 45, 108 and 478 hours on days 8, 15, 22 and 30, resp., after melanoma transplantation. Factors determining the retardation of the melanoma growth rate were analysed. The cell cycle duration recorded on different days after the melanoma transplantation (15--30) was practically unchanged (18--21 hours). The value of the proliferative pool diminished from 71 to 51% on days 15 and 30, resp., after tumor transplantation. The cell loss sharply increased from 51 to 93% between 15 and 30 days of tumor growth. Thus, the retardation of the Harding-Passey melanoma growth was determined substantially by a markedly increased cell loss and, to some degree, by a decreased proliferative pool.
Asunto(s)
Melanoma/patología , Mitosis , Animales , Autorradiografía , Melanoma/metabolismo , Ratones , Trasplante de Neoplasias , Neoplasias Experimentales , Timidina/metabolismo , Factores de TiempoRESUMEN
By means of a autoradiographic method the effect of diazane - a new antitumor substance from the diasoketones class, on the mitotic cycle of leucimia L 1210 has been studied. Diazane in single administration was found to inhibit the development of leucemic process during 2 days. This substance reduces considerably the DNA synthesis intensity in cells, due to that the mitotic activity of cells is markedly reduced. It was demonstrated that diazane during 8 hours blocked the transfer of cells from a presynthetic stage into the DNA synthesis phase. But this substance does not influence the transfer of cells from the premitotic period into mitosis. The substance delayes continuously (during 36 hours) the division of cells being in a phase of the DNA synthesis during its injection. In later terms although multiplication of these cells would be restored, but its intensity is decreased.