Studies of Variation in Oncogenicity of Polyoma Virus Related to Differences in Cell Culture Media

Summary

A variant of polyoma virus with reduced oncogenic potency in mice (M polyoma virus) has been produced by passage of the virus in cultures of P388 D₁ cells grown in a medium containing 20 percent autoclaved nonfat milk. Polyoma virus passaged in P383 D₁ cells grown in medium containing 40 percent human serum (S polyoma virus) had been previously shown by Dawe and his associates to be highly oncogenic in mice. Passage of M polyoma virus in P388 D₁ cells in the 40 percent human serum medium resulted in the conversion of the weakly oncogenic variant to one which was highly oncogenic in mice. After 6 passages of M polyoma virus in serum medium, “polyoma-type tumors” (salivary gland, thymic, and hair follicle tumors) were produced in all of 29 C3Hf/Bi mice inoculated with 10^3.8 tissue culture infectious doses (TCID50); in 34 of 36 mice inoculated with 10^2.8 TCID50; in 19 of 21 inoculated with 10^1.8 TCID50; and in 2 of 17 that received an inoculum containing less than 1 TCID50. In contrast, the original M variant produced salivary gland, thymic, and hair follicle tumors in only 5 of 72 mice inoculated with 10^4.9 TCID50 and in 6 of 42 inoculated with 10^3.8 TCID50. Under the conditions of our plaque-assay system, both M polyoma and S polyoma viruses produced mixtures of small and large plaques. The M variant with low oncogenicity contained 0 to 10 percent large plaques, whereas the highly oncogenic S polyoma virus contained 28 to 50 percent large plaques. Studies of clones derived from large and small plaque types from both the M and S strains will be necessary to determine the relationship of differences in plaque size to the observed differences in oncogenicity.