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Serial intraperitoneal passage of interferon (IFN)-sensitive Friend leukemia cells (FLCs) and L1210-S and RBL-5 tumor cells in syngeneic mice resulted in the selection of tumor cells exhibiting a marked decrease in the capacity to release reverse transcriptase (RT) activity. The virus nonproducer phenotype was a stable characteristic of clones derived from in vivo-passaged IFN-sensitive 745 FLCs. In contrast, in vivo passages of IFN-resistant 3Cl-8 FLCs and L1210-R cells did not result in any significant decrease in the capacity of these tumor cells to release in vitro RT activity. Although in vitro treatment of IFN-sensitive FLCs with mouse alpha/beta IFN (IFN-alpha/beta) for 1 or 10 passages resulted in a marked inhibition in the release of RT activity, these effects were completely reversible after removal of IFN from the culture medium. In addition, in vitro treatment of 745 FLCs with IFN resulted in a marked increase in the expression of H-2 (class I) and gp70 Friend virus antigens on the cell membrane. These effects were not observed in IFN-resistant 3Cl-8 cells. To investigate the possible role of endogenous IFN in the in vivo selection of virus nonproducer tumor cells, IFN-sensitive virus producer FLCs were serially passaged intraperitoneally in mice treated with antibodies to IFN-alpha/beta and in control mice, and the recovered tumor cells were cloned in vitro. Most (83 to 91%) of the clones derived from 745 cells recovered from control mice did not produce any detectable RT activity in the culture supernatants. In contrast, 96% of the clones (26 of 27) derived from 745 cells recovered from mice serially treated with antibodies to IFN-alpha/beta were still capable of releasing high levels of RT activity in the culture medium, indicating that endogenous IFN-alpha/beta was indeed an important host component for the in vivo selection of virus nonproducer tumor cell variants. The results reported in this article indicate that both direct effects of IFN on tumor cells and host-mediated effects are involved in this phenomenon.

journal of virology

Role of endogenous alpha/beta interferon in the selection of virus nonproducer Friend leukemia cells after serial intraperitoneal passages in syngeneic mice