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F Moreau-Gachelin

Publications and source records attributed to F Moreau-Gachelin.

43 records · Page 3Linked to original sources

Emergence of tumorigenic cells during the course of Friend virus leukemias.

Appearance of tumorigenic cells was studied in DBA/2 and ICFW mice infected either with the polycythemia-inducing or the anemia-inducing strain of Friend leukemia virus. Tumorigenicity was defined by transplantability of virus-infected cells into the omentum of an isogeneic preirradiated host. Tumorigenic cells were detected in 50% of the leukemic donors 3 wk after infection by the polycythemia-inducing strain and 7-8 wk after infection by the anemia-inducing strain. These cells appeared first in the spleen and later in peripheral blood, bone marrow, and liver. They consisted of a heterogeneous population at different degrees of malignancy as determined by successive transfers in vivo and in vitro. The observations clearly show that leukemias induced by Friend viruses evolve by multistep processes, in which different stages of malignancy can be detected.

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Detection of tumorigenic cells in Friend virus-infected mice: an in vivo methodological investigation.

Tumor formation by subcutaneous transplants of spleens from erythroleukemic mice infected with Friend virus complex inducing polycythemia (FLV-P) is successful only during the late phase of the disease. To determine whether this observation is due to the absence of tumorigenic cells in the early phase of such leukemia or to the inability of standard procedures to detect these cells, the sensitivities of different routes of inoculation in sublethally irradiated or unirradiated syngeneic recipients were examined. The omentum of the sublethally irradiated mouse was found to be a suitable site for the homing and proliferation of recently isolated tumorigenic cells from FLV-P-infected mice, since it proved 1,000 times more sensitive than the usual subcutaneous sites in unirradiated mice. When this sensitive graft in the omentum was applied to detection of tumorigenic cells in the spleens of FLV-P-infected mice, the mean detection time was 20 days after virus infection, compared to 36 days with the usual subcutaneous graft method.

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Friend leukemia as a multiple-step disease.

The results presented here indicate that erythroleukemia induced by Friend virus evolve by multistage processes. The early phase of Friend disease is characterized by a rapid increase in the number of erythroblastic cells with limited proliferative capacity. The second phase is associated with the appearance of malignant cells with extensive proliferative capacity and autonomous growth. Friend leukemia appears to be a valuable model for studying the sequence of modifications occurring in cells progressing from a normal state to a preneoplastic and finally a highly malignant one.

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Further investigations about actinomycin D action on mouse erythropoietin responsive cell.

Repeated injections of 100 micrograms/kg/day of Actinomycin D entirely eradicated erythropoiesis in normal mice. The study of the effect of graded Actinomycin D doses on the erythropoiesis displayed a reproducible dose-effect relationship. The same relation appeared in the action of various Actinomycin D doses on the response to erythropoietin in hypertransfused-mice. To decide whether Actinomycin D had destructive or inhibitory action on its target cell, myleran was used. A single injection of myleran reduced the pluripotent haematopoietic stem cell (CFU) and the erythropoietin responsive cell (ERC) in polycythemic mice to around 1% that of the controls. When repeated injections of erythropoietin restored a transitory ERC population in the absence of CFU, Actinomycin D to the doses of 90 and 120 micrograms/kg-mouse/day did not prevent the erythropoietin effect on self replication of ERC. This result directly showed that Actinomycin D acted on the ERC by selective inhibition of their differentiation without cytotoxic effect.

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Incapacity of hematopoietic stem cell-deprived mice to produce tumor colonies induced by Friend virus-infected cells.

The role of host hematopoietic stem cells in the formation of tumor colonies in the spleen of (C57BL/6 X DBA/2) F1 mice after grafts of spleen cells from Friend virus (FVP)-infected donors has been investigated. Hematopoietic stem cell compartments of recipient mice were destroyed by Myleran treatment or gamma-ray irradiation. A single injection of Myleran reduced the pluripotent hematopoietic stem cells (CFU) and the erythropoietin responsive cells (ERC) in polycythemic mice to around 1% of that of controls. Repeated injections of erythropoietin (EPO) restored the erythropoietic precursor cell (ERC) population. Pretreatment of polycythemic hosts with Myleran totally suppressed the tumor colony forming ability of grafted Friend virus-infected spleen cells, whereas it had no effect on tumor colonies produced by inoculation of true tumoral Friend cells. After EPO injections in such Myleran-treated recipients, with a consequent appreciable ERC repopulation, splenic colonies again occurred. Similar results were obtained in hosts whose ERC populations were damaged by irradiation. These data strongly suggest that splenic colonies result from the proliferation of the host cells transformed by virus released by Friend virus-infected cells and not from the proliferation of donor tumor cells.

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Stimulation of the biosynthesis of membrane glycoproteins from Zajdela ascites hepatoma cells by Robinia lectin.

Membrane glycoprotein biosynthesis of ascites hepatoma cells is followed by [14C]glucosamine and [3H]leucine incorporation into cells in culture. The rate of incorporation is strongly increased by the addition of Robinia lectin in culture medium. Labeled glycoproteins are released from lectin stimulated and non-stimulated cells by trypsin digestion. Studies of labeled trypsinates on sodium dodecyl sulfate gel electrophoresis and Sephadex G-200 filtration exhibit two fractions both labeled with [14C]glucosamine and [3H]leucine and having different molecular weights, one over 200000 and the other about 2000. Identical results are obtained when external membrane glycoproteins are solubilized by sodium deoxycholate. Comparison of surface glycoproteins isolated by trypsinization from control cells labeled with [3H]-glucosamine and from lectin stimulated cells labeled with [14C]glucosamine displays no significant qualitative differences between glycoprotein fractions released from both cell groups.

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Isolation and characterization of a gp 70+ non producer Friend tumor cell clone.

Viral expression was analyzed in ten cell clones of a Friend erythroleukemia cell line (HFL/b cell line [3]), which had lost its capacity to produce infectious particles. All the ten subclones were non producers but expressed spleen focus forming virus (SFFV) polypeptides in the form of p48-p50gag and gp50-gp52env. One subclone (subclone 9) expressed the gp70env of the Friend-MuLV helper component of the Friend virus complex. Comparative analysis of viral RNA expression in one gp70- subclone (subclone 2) and in the gp70+ subclone (subclone 9) was performed using specific ecotropic env gene probe and MCF/xenotropic env gene probe. In both subclones 2 and 9, the MCF/xenotropic env gene probe detected 32S SFFV genomic RNA, 20S SFFV env gene mRNA and a 34S RNA. The ecotropic env probe failed to characterize any 38S F-MuLV genomic RNA in both clones but detected 34S RNA and 24S env mRNA in the gp70+ subclone 9. These data show that expression of a complete F-MuLV genome is not required for synthesis of env gene products.

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