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Biomedical subjects

F Wendling

Publications and source records attributed to F Wendling.

At least 91 records · Page 5Linked to original sources
PubMed1985

Production of erythropoietin by cloned malignant murine erythroid cells.

A specific immunological assay was used to demonstrate that the erythropoietic factor produced by the recently described FMuLV-induced murine erythroleukemic cell line IW32 is an authentic erythropoietin (epo). Several independent virus-induced erythroleukemic and myeloblastic cell lines were tested for epo production. Among six erythroleukemic cell lines induced by FMuLV, another (NN10) was shown to produce epo by biological and immunological assays. Four Friend-virus-induced erythroleukemias and four FMuLV-induced myeloblastic cells were negative. The amounts of epo produced were similar in IW32 and NN10 supernatants after 48 h in culture. The in vitro bioassay gave the highest levels (up to 1000 mU/ml), the in vivo bioassay the lowest, and the radioimmunoassay gave intermediate results. NN10 and IW32 cell lines have been induced by two different FMuLV and were shown to be independent by cytogenetic studies. The molecular weights of IW32 and NN10 epo were close to the molecular weight of mouse plasma epo but elution profiles suggested that some differences might exist between these epos. Cloned IW32 and NN10 cells were shown to retain both the ability for erythroid differentiation after incubation with chemical inducers and the ability to produce epo. This demonstrates that malignant erythroid cells were the source of epo production in these cell lines.

Animals↗
PubMed1984

Expression of c-ras and c-myc oncogenes in murine erythroleukemias induced by Friend viruses.

We have examined the expression of three cellular oncogenes (c-Ki-ras, c-Ha-ras and c-myc) in different stages of murine erythroleukemias induced in ICFW mice by Friend viruses (F-MuLV and SFFV) in comparison to normal mice spleens and bone marrows, including erythropoietically-stimulated spleens from phenylhydrazine-treated mice. There is no evidence of c-Ki-ras RNA expression in any of the tissues tested. c-Ha-ras RNA was found at similar levels in erythroleukemic cells and normal erythroid cells. In contrast, increased levels of normal 2.3 Kb and short 1.8 Kb c-myc RNA transcripts were detected in both early preleukemic and late leukemic phases of the diseases, as compared to normal erythroid cells. Apparently, neither myc gene amplification nor myc gene rearrangement was observed in erythroleukemias. Our results suggest a possible involvement of c-myc gene either in erythroid cell differentiation or in an early proliferation step of the erythroleukemic process.

Animals↗
PubMed1983

Genesis of a new spleen focus-forming virus: possible role of MCF viruses.

A Friend mink cell focus-inducing (Fr-MCF) virus isolated from a Friend tumor cell line was able to induce acute erythroleukemia associated with polycythemia when injected as a Friend murine ecotropic leukemia virus (F-MuLV) pseudotype into adult Swiss and ICFW mice. One virus isolate recovered from leukemic cells and designated as FV-F3 presented the following properties: (i) persistence of the same leukemogenic power when propagated in vivo and in vitro; (ii) in vivo spleen focus-forming (SFFV) capacity; (iii) presence of erythropoietin (EPO)-independent CFU-E in leukemic animals; (iv) expression of a 32 RNA specifically recognized by a SFFV probe, in FV-F3 infected cells; and (v) expression in FV-F3-infected cell of polypeptides in the range of gp52 SFFV. Peptide analysis of these products revealed close similarities with the parental MCF virus. These data suggest that a SFFV genome arose by genetic recombinational events involving MCF virus.

Animals↗
PubMed1983

Antitumor amino-substituted pyrido[3',4':4,5]pyrrolo[2,3-g]isoquinolines and pyrido[4,3-b]carbazole derivatives: synthesis and evaluation of compounds resulting from new side chain and heterocycle modifications.

New modifications of 10-[[3-(diethylamino)propyl]amino]-6-methyl-5H-pyrido[3',4':4,5]pyrrolo[2,3-g]i sisoquinoline (1b) and 1-[[3-(diethylamino)propyl]amino]-9-methoxy-5,11-dimethyl-6H-pyrido[4,3-b]carba zole (4b), which display important antitumor properties, were performed either on the side chain or on the intercalating heterocycle. Side chains were introduced by direct substitution of the corresponding chloro derivatives and 6-N-methyl-9-hydroxypyrido[4,3-b]carbazoles analogues were prepared via 9-O-benzoyl-1-chloroellipticines. Evaluation of all new compounds shows no significant increase of in vitro cytotoxicity and percent ILS on the L1210 leukemia system by comparison with the model compounds 1b and 4b.

Animals↗
PubMed1983

Production of erythropoietin-like activity by a murine erythroleukemia cell line.

A transplantable murine leukemia, primarily induced by a biologically cloned Friend helper virus, was shown to induce polycythemia in recipient ICFW mice. A leukemia cell line (IW.32) was established in vitro from this transplantable leukemia. Sodium butyrate and hemin induced erythroid differentiation in these leukemia cells as has already been shown with other erythroleukemia cells. The supernatant of this cell line was devoid of spleen focus-forming virus activity. However, it induced the incorporation of 59Fe in polycythemic mice and the in vitro differentiation of murine and human cfu-e into erythroid colonies. Therefore, these erythroleukemia cells produced a factor with all the biological properties of erythropoietin. The erythropoietic activity of IW.32 supernatant was higher in vitro [equivalent to 0.5-1 international unit (IU) of erythropoietin per ml] than in vivo (0.15-0.3 IU/ml). This erythropoietin-like activity was stable at 100 degrees C for 3 min, which ruled out the possibility that a virus was responsible for these effects. Preliminary studies demonstrated that the biochemical properties of the IW.32 factor are strongly similar to those of Connaught step 3 erythropoietin, thus supporting the hypothesis that the IW.32 factor is indeed an erythropoietin.

Animals↗
PubMed1983

[Production of an erythropoietic factor by mouse leukemia].

The graft of a transplantable leukemia (IW 32) induced by a biologically cloned helper of a Friend virus devoid of SFFV activity, was shown to induce a polycythemia in recipient animals. An in vitro continuous cell line was derived from this leukemia. The supernatant was shown to induce an erythroid differentiation both in vivo in Mice rendered polycythemic by transfusion, and in vitro in plasma clot CFUE assay. This erythropoietic activity was heat stable (30 min. 56 degrees C, 3 min. 100 degrees C) which ruled out the hypothesis that the IW 32 cell line produced a polycythemia inducing virus. The erythropoietic factor produced by IW 32 leukemic cells might be erythropoietin.

Animals↗
PubMed1981

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.

Animals↗
PubMed1981

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.

Animals↗
PubMed1981

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.

Animals↗
PubMed1980

Structure-activity relationships in a series of newly synthesized 1-amino-substituted ellipticine derivatives.

The synthesis of a series of 1-amino-substituted pyrido[4,3-b]carbazole derivatives, based on the substitution of corresponding 1-chloroellipticines, is reported. The cytotoxic properties on tumor cells grown in vitro, the in vivo acute toxicity of the most potent in vitro cytotoxic compounds, and the antitumor properties toward the L1210 leukemia system are described. No correlation between the apparent association constant to DNA and the in vitro cytotoxicity or the in vito antitumor efficiency could be observed in this series. 9-Hydroxylated derivatives were more cytotoxic in vitro than the corresponding 9-methoxylated compounds. However, their antitumor efficiencies on the in vivo experimental systems do not confirm the advantage of demethylation. The presence of a [(dialkylamino)alkyl]amino side chain at the 1 position of ellipticines increases the antitumor potency: 1-[[3-(diethylamino)propyl]amino]-5,11-dimethyl-6H-pyrido[4,3-b]carbazole (5) is a very potent antitumor compound (% ILS of 134 on the L1210 leukemia system).

Alkaloids↗
PubMed1979

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.

Animals↗
PubMed1978

Oncogenicity of Friend-virus-infected cells: determination of origin of spleen colonies by the H-2 antigens as genetic markers.

Spleen cells from mice infected with Friend leukemia virus (FLV) inoculated by the intravenous route give rise to macroscopically visible colonies in the spleens of normal F1 histocompatible hybrid hosts. A study of H-2 antigens as generic markers for identification of strains of origin of cells constituting the spleen colonies was undertaken. The standard cytotoxic test was demonstrated to be suitable for characterizing the H-2 antigens present on the surface of spleen cells from normal of FLV-leukemic parents of F1 hybrid mice. Individual colonies dissected out of the spleen of (C3HxC57B6/6) F1 recipients (H-2k/H-2b), 10 days after the intravenous graft of FLV-infected spleen cells of C3H origin (H-2k), were all sensitive to anti-C57BL/6 antibodies. In the same way, colonies obtained from the spleens of (DBA/2xC57BL/10) F1 recipients (H-2d/H-2b) grafted with DBA/2 leukemic spleen cells (H-2d) were all sensitive to both anti-H-2b and anti-H-2d antibodies. These results directly prove that the main cell population constituing a spleen colony arises from the recipient. The authors conclude that the spleen colonies do not result from the neoplastic proliferation of injected donor cells but rather from the multiplication of host cells transformed by Friend virus produced by the grafted cells.

Animals↗
PubMed1978

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.

Animals↗
PubMed1977

[Cytotoxic and antitumor activity of a new series of heterocyclic compounds: dipyrido (4,3-b) (3,4-f) indoles].

Among newly synthesized compounds derived from the dipyrido [4,3-b] [3,4-f] indole nucleus, two have proved to be particularly active in vitro and in vivo. Their cytotoxic effects on cultured cells have been determined. At non toxic doses, they displayed a pronounced inhibitory effect on experimental L1210 Leukemia. These compounds have a strong affinity for DNA molecules.

Animals↗
PubMed1975

Target cell of the polycythemia-inducing Friend virus: studies with myleran.

A single injection of Myleran reduced the pluripotent hematopoietic stem cell, i.e., colony forming unit(s) (CFU), and the erythropoietin-responsive cell (ERC) in polycythemic mice to around 0.5% that of the controls. Repeated injections of erythropoietin (EP) restored ERC populations, whereas the CFU remained at very low levels. This selective action of Myleran and EP in polycythemic mice seemed to be a good approach for the study of oncogenic action of Friend virus on target cells. When the CFU and ERC compartments were decreased, practically no response to the virus was obtained. When there was an appreciable ERC population present with decreased CFU, leukemogenesis still occurred (as judged by the increased spleen weight). This result was in proportion to the dose of EP, i.e., stimulation of the ERC or closely related cells.

Animals↗