The production of a type D retrovirus (PMFV) was analysed using different conditions of cultivation. Both in cell culture flasks and in roller culture bottles with discontinuous change of medium an increase of virus amount was determined within 12 h after seeding of virus-infected cells. Then the virus production considerably fluctuated around an apparent mean value until the end of the experiment at 56 h. In case of a continuous change of cell culture medium in roller bottles a maximum of virus production was measured at a retention time of 24 h of cell culture medium. The production of PMFV could be essentially increased when virus-producing cells were co-cultivated with non-infected cells of the same type.
Mason-Pfizer monkey virus (MPMV) and an MPMV-like virus (PMFV) detected in a human continuous cell line were compared in immunofluorescence tests. Antisera against MPMV and PMFV revealed cross-reacting antigens in the cytoplasm of cells infected with either MPMV or PMFV. Immunofluorescence absorption showed that, in addition to the common specificities, both viruses have distinct antigens. MPMV and PMFV must therefore be regarded as different types of a closely related virus group.
1. Application of hamster papova virus to newborns of Syrian hamster has produced some s.c. sarcomas after a 5 to 6 month latency period, by virtue of the strong inducer effect of this papova virus to endogenous (latent) oncorna viruses. 2. Cellfree filtrates from a polymorphorus-cell sarcoma produced in this way, when applied to newborn hamsters of the spontaneously tumour-free hamster line HaP, again lead to sarcoma formation after a latency period of 3--8 months in about 20% of the animals; the same holds for cellfree filtrates of these cellfree induced sarcomas and their transplantation generations. 3. In these tumours C-type oncorna viruses, but no papova virus, could be demonstrated regularly. 4. The hamster specificity of this sarcoma virus is suggested by the complete absence of a tumorigenic effect of the cellfree filtrates from these hamster sarcomas in mice and rats. The preferential induction of hamster sarcomas by sarcoma filtrates, in conjunction with the fact that filtrates from hamster leukoses, indicates a certain difference between hamster leukemia and hamster sarcoma viruses.
Morphological studies on sarcomas induced in syrian hamsters by cellfree transmission are described. The tumour tissue for the cellfree preparations stemmed from a sarcoma, containing C-particles. Basically, three histological groups have been distinguished: 1. neoplasms of the peripheral nerve-sheath, 2. undifferentiated sarcomas, and 3. liposarcomas. Furthermore, a rhabdomyosarcoma, an angiosarcoma and, in a heterotransfection on rat, an osteosarcoma have been established. The great majority of tumours could be transmitted by cellfree preparations. To this neoplasms belong the undifferentiated histological structure.
A virus of the paramyxo-type was eliminated from cell-free material of human oncornavirus-producing cell lines (PMF). After transmission of this paramyxovirus-free inoculum to a human permanent cell strain (Tu 197/Tr 1) oncornaviruses were permanently formed and no paramyxoviruses could be detected. The paramyxovirus-free, oncornavirus-producing PMF-39 cell line could be established after inoculation of the TU 197/Tr 1 line with cell-free material containing both oncorna- and paramyxovirus diluted 1 to 1000. A second way of elimination of the paramyxovirus was the treatment of cell-free material containing both viruses with antisera against paramyxovirus. In the Tu 197/Tr 1 line inoculated with such material only oncornaviruses were formed. The second paramyxovirus-free oncornavirus-producing cell line was designated PMF 50.
Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.
Immunodiffusion analysis of the PMF virus which was detected in malignant permanent human cell lines revealed positive reactions with antisera against the Mason-Pfizer monkey virus (MPMV). No cross-reactivity was demonstrated with murine leukemia virus (MuLV), rat leukemia virus (RaLV), hamster leukemia virus (HaLV), feline leukemia virus (FeLV), simian (woolly monkey) sarcoma virus (SSV-1) and mouse mammary tumor virus (MTV). The cross-reactive antigens of the PMF virus and the MPMV are considered as evidence for the human origin of the PMF virus.
In this article is reported a generalized leukemia of the myeloproliferative system of golden hamsters capable of cellular transmission. Cellfree transmissions to 83 golden hamsters after a 6-month latency period, have so far yielded the same result in three cases. After cellular transplantation leukocyte counts of 180,000 on the average occured abruptly in the end-phase of the disease. Latencies were between 4 and 10 days. Electronmicroscopically, oncorna-viruses were demonstrated in hamsters inoculated with either the cellular or the cellfree preparation that bear close resemblance to the murine C-particles.
Results on morphologic and hematologic characterization of a hamster leukemia capable of both cellular and cellfree transmission are described. Solid tumors removed in the course of several passages of leukemia animals, after producing blood smears, and spleen, liver, lymph nodes, bone marrow, thymus, kidney and lung were investigated histologically and histochemically. The morphological picture of the hamster leukemia has not changed during several transplantation generations. In addition to solid tumours, typical leukemic infiltration were detected histologically in spleen, liver, lymph nodes, bone marrow, kidneys and lung. No leukemic proliferation was noticed in the thymus. The final stage of the disease is characterized by an abrupt occurrence of high leukemic cell counts. The demonstration of alkaline phosphatase, but especially of naphtol-AS-D-chloroacetate esterase, in the leukemic cells is interpreted as indicating malignization of cells of the granulocytic line.
A melanin containing skin tumour of trichoepitheliomatic character, induced by a virus some 40 nm large, is described showing neither infiltrative nor metastasizing growth. The multiple, flat, mostly confluent tumour nodes appear in all parts of the skin, especially in dorsal skin, at the chin, eyes, and ears. The tumours are mostly blue black as a result of hemosiderin and melanin deposits; these pigmentations occur in connective-tissue cells, the tumour cells and the abounding keratinizing cysts. The blastomic character of these tumours, which in part are reminiscent of tricho-epitheliomas, can be demonstrated by transplantation experiments, in which with increasing number of passages are observed a decrease of latent period, disappearance of pigment formation, and increase in histologic de-differentiation.
Evidence is presented for the presence of C-type-like particles in the syncytiotrophoblast of normal human placentas. In 10 of 110 mainly immature placentas studied both extracellular and budding particles were found.