Several long-term cultures were established from a spontaneous melanoma of a cat. Cells were rounded or spindle shaped and exhibited black/brown pigmentation in the cytoplasm. No virus was released from these cells spontaneously or after treatment with chemicals. However, exogenous infection of the cat melanoma cells with the endogenous cat virus RD114 resulted in remarkable morphological and functional changes. Most of the RD114 virus-infected cells exhibited multiple neuritic extensions and about 1-2% of the population showed characteristics of neuronal cells. Because human, mouse, and hamster melanoma cultures infected with various mammalian retroviruses, including the RD114 virus, did not display any morphological alteration, it is concluded that the neuronal cell differentiation in the cat melanoma cells is a consequence of its specific interaction with the endogenous cat retrovirus.Retroviruses are ubiquitous in nature and are associated with a large variety of neoplasms in their natural hosts (1,2 viruses (20). Other viruses included rat leukemia virus (RaLV), hamster leukemia virus (HaLV), simian sarcoma-associated virus (SSAV), squirrel monkey virus (SMV), Mason-Pfizer monkey virus (MPMV), several strains of feline leukemia viruses (FeLV), and baboon and cat endogenous viruses (BaEV and RD114, respectively) (12, 21-28).Duplicate sets of human, cat, mouse, and hamster melanoma cultures were plated at a density of 106 cells per 25-cm2 flask in media containing Polybrene at 4 tkg/ml and were exposed separately to a multiplicity of infection (moi) of =':1 for each of the viruses listed in Table 1. Cells were examined for morphological changes and virus replication was judged in the culture fluids by the presence or absence of reverse transcriptase activity as described (29). The MuLV, FeLV, and RD114 virusinfected cells also were examined by immunofluorescence assay for the virus p30 antigens by the use of respective fluorescein isothiocyanate-conjugated antiserum (30).Neural-Specific Staining. Monolayer cultures of virus-exposed and unexposed control cells were fixed in 95% methanol and stained by the silver impregnation method (15). Treatment of Melanoma Cells with Chemicals. To investigate whether chemicals can induce neuronal cell differentiation in the cat melanoma cultures, epithelial growth factor (EGF), cAMP, theophylline, 5-iododeoxyuridine (IdUrd), dimethyl sulfoxide (Me2SO), hypoxanthine, aminopterin, and tumor proAbbreviations: MuLV, murine leukemia virus; RaLV, rat leukemia virus; HaLV, hamster leukemia virus; SSAV, simian sarcoma-associated virus; SMV, squirrel monkey virus; MPMV, Mason-Pfizer monkey virus; FeLV, feline leukemia virus; BaEV, baboon endogenous virus; EGF, epithelial growth factor; Me2SO, dimethyl sulfoxide; TPA, 12-0-tetradecanoylphorbol 13-acetate; moi, multiplicity of infection; araC, 1-,B D-arabinofuranosylcytosine.
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