RESUMEN
We studied physiological parameters of rhesus monkeys after administration of anthracycline antibiotic doxorubicin. Intravenous administration of the drug caused intoxication manifested in in an abrupt body weight loss, baldness, vomiting, and exicosis. Intoxication in monkeys determined by the damaging effects of doxorubicin on organs and tissues is also characterized by significant changes in the blood: leukopenia, thrombocytopenia, neutropenia, monocytopenia, lymphocytosis, and a sharp drop of CD20+ B cell content. The total protein and albumin content in the blood significantly decreased. A sharp increase in C-reactive protein was also accompanied by an increase in activity of proinflammatory cytokine IL-6. Transplantation of mesenchymal stem cells in some cases can significantly alleviate doxorubicin-induced damage to organs and maintain normal clinical status of monkeys after two injections of the drug. Late transplantation of stem cells does not have a protective effect and does not protect the animals from the damaging effects of doxorubicin. We found that the protective effect of mesenchymal stem cells depends on the dose of the drug, total number of cells, and the time of their transplantation. It should be noted that human and monkey mesenchymal stem cells produce similar regenerative effects, at least in the doxorubicin toxicity model.
Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Alopecia/inducido químicamente , Animales , Peso Corporal/efectos de los fármacos , Proteína C-Reactiva/metabolismo , Humanos , Interleucina-6/metabolismo , Macaca mulatta , MasculinoRESUMEN
Three injections of doxorubicin to rhesus macaques cause severe intoxication, characterized by anemia, cachexia, and degeneration of the viscera. The life span of monkeys injected with the drug and receiving after 24 h mesenchymal stem cell transplantation varied from 96 to 120 days in comparison with 50-74 days in animals receiving stem cells before doxorubicin. Controls received doxorubicin and saline; the lifespan of one monkey was 24 days, of the other - 1 year and 8 months. The increase in activity of proinflammatory cytokine IL-6 was paralleled by an increase in the level of C-reactive protein.
Asunto(s)
Doxorrubicina/efectos adversos , Células Madre Mesenquimatosas/fisiología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Citocinas/metabolismo , Interleucina-6/metabolismo , Macaca mulatta , Trasplante de Células Madre Mesenquimatosas , Células Madre/efectos de los fármacos , Células Madre/metabolismoRESUMEN
Four lymphoid cell cultures obtained from Papio hamadryads with malignant lymphomas were studied. The cultured cells produced two lymphotropic EBV-like herpes virus of Papio (HVP) and T-lymphotropic monkey retrovirus STLV-1 (HTLV-1 family) or HVP alone. More than 100 subcultured cell lines were shown to remain mixed B- and T-cellular, the levels of T cells of different subpopulations were 15-50%. Cytogenetic investigations showed that one of the 4 cultures was tumorogenic and the others were derived from the normal cells of monkeys with malignant lymphomas. It is suggested that the presence of a cultural virus (viruses) may affect the karyotypes of cells.
Asunto(s)
Linfocitos B/virología , Herpesvirus Cercopitecino 1/aislamiento & purificación , Linfoma/patología , Papio , Virus Linfotrópico T Tipo 1 de los Simios/aislamiento & purificación , Linfocitos T/virología , Animales , Linfocitos B/patología , Infecciones por HTLV-I/patología , Infecciones por HTLV-I/veterinaria , Infecciones por HTLV-I/virología , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Linfoma/veterinaria , Linfoma/virología , Linfocitos T/patología , Células Tumorales CultivadasAsunto(s)
Papio , Linfocitos T/patología , Animales , Aberraciones Cromosómicas , Diploidia , Cariotipificación , Tejido Linfoide/patología , Linfoma de Células T/genética , Linfoma de Células T/patología , Linfoma de Células T/veterinaria , Enfermedades de los Monos/genética , Enfermedades de los Monos/patología , Papio/genética , Linfocitos T/ultraestructura , Células Tumorales CultivadasRESUMEN
Permanent suspension B-cell lines HSL-1, HSL-2, HSL-3, HSL-4, HSL-5, HSL-8, HSL-9 have been obtained spontaneously from lymphocytes and cells of hematopoietic tissues of patients with various forms of leukemia and tumours. All cell lines contained Epstein-Barr virus (EBV). At early stages of cultivation (6-39th passages) normal karyotypes were established for all the tested lines which testified their origin from normal B-lymphocytes. In the process of cultivation of HSL-1 cell line, which (up to the 63rd passage) contained primarily the normal karyotypes, a substitution for tetraploid ones (92, XX, YY) by the 132nd passage was established. In line HSL-4, a pathological clone of cells with structural chromosome rearrangements (46, XY, -2, -12, der (12) t (2; 12) (p12, p13); del2 (p12), was revealed at the 26th passage. During a prolonged cultivation (up to the 130th passage) this abnormal clone forced out completely the clone with normal karyotype. Substitution of normal clone cells by cells with pathological karyotypes may point to their selective advantage.
Asunto(s)
Linfocitos B/ultraestructura , Aberraciones Cromosómicas , Bandeo Cromosómico , Herpesvirus Humano 4 , Enfermedad de Hodgkin/patología , Humanos , Cariotipificación , Leucemia Mieloide Aguda/patología , Neoplasias Pulmonares/ultraestructura , Metafase , Región Organizadora del Nucléolo/ultraestructura , Factores de Tiempo , Células Tumorales CultivadasRESUMEN
A cytogenetic analysis of 9 permanent suspension cell lines was performed. Cell lines were obtained from Papio hamadryas and Macaca arctoides cells by different methods. Five cell lines originated from non-malignant parental cells. Lines SPG-5 and SPG-6 were analysed at early stages of cultivation, with normal karyotypes being identified. In cell lines PL-11, MAL-1 and MAL-4 pathological clones with structural and numerical chromosomal rearrangements appeared only following a long-term cultivation. This phenomenon may be due presumably to the influence of cultivation on karyotype variability. In cell line LUG-4 chromosome marker 17p+ was found at early stages of cultivation. In sublines E9-1, E1-1 and E5-1, established from line LUG-4 by cloning, 17p+ chromosomal marker was found persisting. The presence of the marker 17p+ in all the cells at early passages testifies that the cell material from Papio with lymphoma, which was used for this line, might have the same chromosomal damage in its initial karyotype.