Morphological, biological, immunological and biochemical studies on bone tumors of animals and man.

Biological studies on FBJ osteosarcoma virus in tissue cultures have led to the isolation of murine sarcoma virus. Characteristic type C-MuLV particles were observed in bone tumors induced by the SD-MSV-M-virus in vitro and in vivo. The SD-MSV-M virus also induced bone tumors in rats of all strains tested, and it has a similar tumor-inducing property in hamsters. Immunoelectronmicroscopic studies showed that envelope antigens of MSV-SD virus in rat bone tumors can be distinguished from those found in hamster bone tumor cells. In tissue cultures of MSV-SD rat bone tumors, two separate cell lines have been established: one of them releases both MSV and MuLV and the other produces MuL virus only. The MuLV in this cell line acts as helper. The different interactions appear to support the concept of control mechanisms for the partial expression of genes which are responsible for neoplastic properties, virus replication, and synthesis of gs-antigens. Biochemical studies on structural rearrangement and subunit composition of RNA released from MSV-SD virus, have shown that there are two forms of the native genome RNA differing in their sedimentation coeffiiecients and in subunit composition. In human osteosarcoma tissue culture, type-C viruslike particles are found. In cocultures derived from human osteosarcoma with cells taken from the bone marrow or peripheral blood of patients with different types of leukemia, certain morphological changes are observed which resemble those induced in animal cells by RNA tumor viruses. In osteosarcomas where no cytoplasmic antigen could be proved by an immunofluorescence test, the antigen could be produced by cocultivation with antigen-positive leukemic bone marrow cells. Whole human embryo cells treated with fluid from leukemia bone marrow cultures showed the presence of the cytoplasmic antigen when tested with positive sera, but they showed no morphologic changes. In high molecular weight RNA species, sedimentation coefficients ranging from 62S to 68S are demonstrated by molecular hybridization techniques. In cross-hybridization experiments, annealing values were observed only with complementary DNA products synthesized from sarcoma viruses. Three particularly high molecular weight RNA species released from human sarcoma cell cultures showed no cross-hybridization with either the DNA product of Rauscher leukemia virus or that of Gross leukemia virus.