Endogenous oncornaviruses in chemically induced transformation. II. Effect of virus production in vivo.

C3H/HeJ and AKR/J mice differed in their susceptibility to 3-methylcholantrhene (MCA)-induced sarcomagenesis (86% incidence of sarcomas in C3H by 18 wk; 5% incidence in AKR by 18 wk) and in the production of endogenous murine leukemia virus (MuLV) (AKR produced greater than 10(5) plaque-forming units/ml tail extract in XC test; C3H did not produce detectable virus.) A genetic corss between C3H and AKR mice was examined to determine the relationship of virus production to oncogenesis by MCA. Mice of the (C3H X AKR)F X C3H backcross were typed for the production of infectious MuLV by tail biospy and then inoculated with MCA. Of the backcross mice, 81% produced high titers of ecotropic MuLV; the remaining 19% did not contain detectable infectious MuLV. The virus-producing and non-virus-producing backcross mice were equally sensitive and highly susceptible to MCA-induced sarcomagenesis. Tumors of all virus-positive mice contained infectious MuLV. Some tumors (54%) of virus-negative mice also contained infectious MuLV; this indicated the induction of endogenous MuLV in the tumors of these mice. We concluded that the overt production of MuLV in mice of this backcross did not function in the sensitivity of the mice to sarcoma induction by MCA. Furthermore, the presence of virus in some chemically induced tumors was due to an induction pehnomenon independent of the primary oncogenic event.