Animal virus screens for potential teratogens. I. Poxvirus morphogenesis.

The growth of poxvirions in cell culture is considered a teratogen screening test, since this virus has a rapid, simple morphogenetic pathway that is dependent upon cell proliferation. Vaccinia WR-infected BSC 40 monolayers were exposed to 42 known teratogens and 9 nonteratogens at dosages from 1 microM to 100 mM. After 24 h of infection, the number of functional virions was determined by plaque assay. Thirty-three of the 42 teratogens inhibited the virus, 3 teratogens stimulated the virus, and 6 teratogens were false-negatives. Eight of the 9 nonteratogens had no effect on virus proliferation at dosages as high as 600 times the lowest reported teratogenic dosage. The number of new virions could be directly related to the concentration of the teratogen in vitro, thus allowing each compound to be characterized by an RD50. The RD50 dosage in milligrams per liter was 98% correlated with the lowest reported teratogenic dose in vivo in milligrams per kilogram. In sum, vaccinia-infected cells have an easily identifiable endpoint, plaque-forming units, which may be an accurate prognosticator of teratogenesis.