Malignant S49 mouse lymphoma cells that grow in suspension culture demonstrate in their cytoplasm characteristic tubular structures. These structures also appear in immunogenic, substrate-adherent variants of S49 cells that grow in culture. Upon transfer of both cell types into nude mice, the tubular structures of the adherent variants (and not the suspension-growing cells) undergo a profound alteration whereby their tubular components disappear and clusters of viruslike particles appear. These very closely resemble, on morphological grounds, precursors of B-type retroviruses. This specific in vivo interaction between the host and the S49 variant can be mimicked in culture by treatment of these cells for 24 h with 500 U/ml of mouse interferon. The suspension-growing S49 cells are unresponsive to interferon in this respect. Immunohistochemical analysis reveals that both tubular structures and the viruslike particles represent stages in the morphogenesis of mouse mammary tumor virus. A working hypothesis is advanced relating the regulation of the tubular system to the impaired tumorigenic potential of adherent S49 cells in syngeneic Balb/c hosts.

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