scholarly journals EVIDENCE FOR TRANSFORMATION OF SPLEEN CELLS ONE DAY AFTER INFECTION OF MICE WITH FRIEND LEUKEMIA VIRUS

1970 ◽  
Vol 131 (4) ◽  
pp. 765-781 ◽  
Author(s):  
Giovanni B. Rossi ◽  
Gustavo Cudkowicz ◽  
Charlotte Friend
Keyword(s):  
Leukemia Virus ◽  
Erythroid Differentiation ◽  
Growth Potential ◽  
Leukemic Cells ◽  
F1 Hybrid ◽  
Hemopoietic Cells ◽  
Friend Leukemia ◽  
Friend Leukemia Virus ◽  
Marrow Cells

Proliferation and erythroid differentiation of transplanted DBA/2 marrow cells and Friend virus-induced leukemic cells were assessed in syngeneic, allogeneic (H-2 compatible), and (BALB/c x DBA/2)F1 hybrid mice (CDF1). Measurements were made 5 days after transplantation of donor cells into nonirradiated or X-irradiated mice by the spleen colony or the 125IUdR-59Fe uptake methods. Growth of DBA/2J (Jackson subline) marrow grafts was poor in irradiated CDF1J hybrids as compared with growth in syngeneic and allogeneic hosts. The DBA/2J transplants proliferated, however, without impairment in irradiated CDF1 hybrids which were the progeny of DBA/2 male parents of other sublines, e.g. DBA/2Ha, DBA/2Cr, and DBA/2Cum. In contrast, tissue-cultured Friend leukemic cells of DBA/2J origin grew deficiently in all CDF1 hybrids tested, regardless of irradiation and of the DBA/2 parent's subline. The growth pattern of transplanted DBA/2J cells was a manifestation of hybrid resistance. The results with DBA/2J and other DBA/2 subline grafts suggested that hybrid histocompatibility alleles were expressed to a greater extent in leukemic than in normal marrow cells, for the former were consistently recognized as "nonself" by CDF1 mice, but not the latter cells. The property of deficient growth in irradiated CDF1Ha hybrids was acquired by DBA/2J hemopoietic cells within 6 hr from infection in vivo with Friend leukemia virus, and persisted during the following 8 days. It was ascribed to enhanced expression of hybrid histocompatibility gene(s) (Hh) induced by the virus. Autonomous growth potential of hemopoietic cells, manifested by proliferation in nonirradiated recipients, was first detected 24 hr from infection, and likewise persisted at the later intervals. At the same time, the infected cells grew deficiently also in nonirradiated CDF1Ha mice. The two irreversible cellular changes were regarded as the earliest signals of virus-induced transformation.

scholarly journals Friend Leukemia Virus Infection Enhances DNA Damage-Induced Apoptosis of Hematopoietic Cells, Causing Lethal Anemia in C3H Hosts

2002 ◽  
Vol 76 (15) ◽  
pp. 7790-7798 ◽  
Author(s):  
Masanobu Kitagawa ◽  
Shuichi Yamaguchi ◽  
Maki Hasegawa ◽  
Kaoru Tanaka ◽  
Toshihiko Sado ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dna Damage ◽  
Knockout Mice ◽  
Bone Marrow Cells ◽  
Leukemia Virus ◽  
Hematopoietic Cells ◽  
Friend Leukemia ◽  
C3h Mice ◽  
Friend Leukemia Virus ◽  
Marrow Cells

ABSTRACT Exposure of hematopoietic progenitors to gamma irradiation induces p53-dependent apoptosis. However, host responses to DNA damage are not uniform and can be modified by various factors. Here, we report that a split low-dose total-body irradiation (TBI) (1.5 Gy twice) to the host causes prominent apoptosis in bone marrow cells of Friend leukemia virus (FLV)-infected C3H mice but not in those of FLV-infected DBA mice. In C3H mice, the apoptosis occurs rapidly and progressively in erythroid cells, leading to lethal host anemia, although treatment with FLV alone or TBI alone induced minimal apoptosis in bone marrow cells. A marked accumulation of P53 protein was demonstrated in bone marrow cells from FLV-infected C3H mice 12 h after treatment with TBI. Although a similar accumulation of P53 was also observed in bone marrow cells from FLV-infected DBA mice treated with TBI, the amount appeared to be parallel to that of mice treated with TBI alone and was much lower than that of FLV- plus TBI-treated C3H mice. To determine the association of p53 with the prominent enhancement of apoptosis in FLV- plus TBI-treated C3H mice, p53 knockout mice of the C3H background (C3H p53−/− ) were infected with FLV and treated with TBI. As expected, p53 knockout mice exhibited a very low frequency of apoptosis in the bone marrow after treatment with FLV plus TBI. Further, C3H p53−/− → C3H p53+/+ bone marrow chimeric mice treated with FLV plus TBI survived even longer than the chimeras treated with FLV alone. These findings indicate that infection with FLV strongly enhances radiation-induced apoptotic cell death of hematopoietic cells in host animals and that the apoptosis occurs through a p53-associated signaling pathway, although the response was not uniform in different host strains.

scholarly journals Cell-free transmission of Fv-4 resistance gene product controlling Friend leukemia virus-induced leukemogenesis: a unique mechanism for interference with viral infection

Blood ◽  
1995 ◽  
Vol 86 (4) ◽  
pp. 1557-1563 ◽  
Author(s):  
M Kitagawa ◽  
S Aizawa ◽  
H Kamisaku ◽  
H Ikeda ◽  
K Hirokawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mononuclear Cells ◽  
Specific Binding ◽  
Leukemia Virus ◽  
Spleen Cells ◽  
Peripheral Blood Mononuclear ◽  
Friend Leukemia ◽  
Bone Marrow Chimeras ◽  
Friend Leukemia Virus

Fv-4 is a mouse gene that dominantly confers resistance to infection by ecotropic murine leukemia virus (MuLV). We previously demonstrated that mixed radiation bone marrow chimeras containing Fv-4r-bearing BALB/c-Fv- 4Wr (C4W) bone marrow and Fv-4r-bearing C3H/He (C3H) bone marrow grafted into C3H recipient mice (C4W+C3H-->C3H) were resistant to Friend leukemia virus (FLV)-induced leukemogenesis, even when they contained as high as 70% C3H-derived cells. This indicates that FLV- sensitive C3H-derived cells are rendered refractory to infection and/or transformation with FLV when they coexist in mice with Fv-4r-bearing cells. To investigate the mechanism of Fv-4 resistance to FLV-induced leukemogenesis, we first examined the expression of Fv-4r env antigen in the peripheral blood mononuclear cells (PBMC) of these chimeras. The Fv-4r env antigen was present not only on C4W-derived cells, but also on Fv-4r-bearing C3H-derived cells in C4W+C3H-->C3H mixed bone marrow chimeras. The Fv-4r env antigen that binds to the cells surface of C3H cells was found in sera from normal C4W mice, C4W-->C3H chimeras, and C4W+C3H-->C3H mixed chimeras. The serum Fv-4r env antigen binds to ecotropic MuLV receptors, shown by specific binding to transfectant mink cells expressing ecotropic MuLV receptor, but not to parental mink cells. To determine whether the binding of Fv-4r env antigen to the putative MuLV receptors would block FLV infection, C3H thymocytes or spleen cells that had been preincubated with C4W serum were mixed with FLV and the subsequent production of MuLV specific antigens was examined. C3H thymocytes or spleen cells treated with C4W serum became refractory to binding by FLV. These results provide evidence that the Fv-4r env antigen is released from C4W-derived cells in vivo and binds to cells expressing surface receptors for ecotropic MuLV, thereby protecting them from infection with FLV. The implication of these findings for gene therapy of retrovirus-induced disease such as acquired immune deficiency syndrome (AIDS) is discussed.

scholarly journals Long-term culture of bone marrow-derived preleukemic cells from F-MuLV- infected mice

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 193-199
Author(s):  
JM Heard ◽  
B Sola ◽  
MA Martial ◽  
S Fichelson ◽  
S Gisselbrecht
Keyword(s):  
Bone Marrow ◽  
Cell Lines ◽  
Bone Marrow Cells ◽  
Leukemia Virus ◽  
Friend Leukemia ◽  
Normal Sensitivity ◽  
Friend Leukemia Virus

The replication-competent Friend leukemia virus (F-MuLV) induces leukemias involving three hematopoietic lineages after a latent period of several months. In an attempt to elucidate the early events of the leukemogenic process, we looked for a method allowing the isolation and the long term in vitro maintenance of preleukemic cells. When established as long-term cultures according to the technique described by Dexter et al, bone marrow cells obtained from 7/7 apparently healthy F-MuLV-infected preleukemic mice led to the accumulation of immature myeloblastic cells, and to the generation of permanent myeloblastic cell lines, which in most cases further became tumorigenic in preirradiated recipient animals. The delays required to obtain cell lines were shorter when the duration of the in vivo infection was longer, suggesting that these cells were committed into the leukemogenic pathway before their transfer into culture flasks. The myelomonocytic preleukemic cells exhibited normal sensitivity to purified preparations of CSFs, but acquired the capacity to grow in the absence of exogenous CSF stimulation. Examination of integrated provirus copies demonstrated that the preleukemic cell proliferation involved a single or a few clones which may progress in vitro from a preleukemic to a fully malignant stage without major modifications of the integrated provirus copies.

scholarly journals Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells.

1976 ◽  
Vol 143 (2) ◽  
pp. 305-315 ◽  
Author(s):  
S Sassa
Keyword(s):  
Enzyme Activities ◽  
Biosynthetic Pathway ◽  
Aminolevulinic Acid ◽  
Leukemia Virus ◽  
Erythroid Differentiation ◽  
Inhibitory Effect ◽  
Friend Leukemia ◽  
Ala Synthetase ◽  
Friend Leukemia Virus ◽  
Sequential Induction

The process of erythroid differentiation in mouse Friend leukemia virus transformed cells (T3-C1-2) was examined by following changes in several enzyme activities of the heme biosynthetic pathway and in heme concentration while the cells were undergoing erythroid differentiation after treatment with dimethylsulfoxide. Untreated cells on the one hand, have a limited capacity for spontaneous differentiation. On the other hand, dimethylsulfoxide(DMSO)-treated cells showed an increase in the activities of delta-aminolevulinic acid (ALA) synthetase, ALA dehydratase, uroporphyrinogen-I synthetase, ferrochelatase, and heme concentration by days 1, 1.5, 2, and 4, respectively. The increase of the heme pathway enzymes and heme concentration followed the order of these enzymes or products as they are arranged in the heme biosynthetic pathway. These changes induced by DMSO were effectively inhibited by treatment with actinomycin D, suggesting that continued RNA synthesis is required for the differentiation process. 5-bromo-2'-deoxyuridine (BrdU) (10(-5) M) inhibited the DMSO-induced changes of the heme pathway enzymes. BrdU was most effective when it was present during the first 2 days of cell culture. It gradually lost its inhibitory effect when added after the 3rd day or later. The BrdU-mediated inhibition was completely overcome by the addition of thymidine (7 x 10(-5) M), but not by uridine (7 x 10(-5) M). All these data suggest that a sequential induction of the heme pathway enzyme takes place during erythroid differentiation of Friend leukemia cells, and that the sequential induction of the enzymes may be due to a sequential activation of genes coding for these enzyme activities.

Sign in / Sign up

Export Citation Format

Share Document