Tumorigenicity, Immunogenicity, andVirusProduction inMouseMelanoma Cells Treated with5-Bromodeoxyuridine (murine leukemia virus/helper virus/tumor suppression/antigens/electron microscopy)

Bromodeoxyuridine (BrdU), whetherad- ministered ina30-hrpulseof30Mg/mlorcontinuously in lowconcentrations (1-3 ug/ml), significantly increased pro- ductionofparticles withthemorphology ofmurineleu- kemiavirus inamousemelanoma(B16) cell line. Particles wereveryrareincontrol cells, detectable onlybyelectron microscopy. Bycontrast, inmanyexperiments withBrdU- treated cells thenumbersofvirusparticles countedby electron microscopy increased over100-fold, and other tests formurineleukemia virus(plaque assayandtests for group-specific antigens 1and3andforGrosscell-surface antigens) becamepositive. AllBrdU-treated cells, regard- lessofdrugconcentration orlengthoftreatment, inaddi- tiontoshowinglossofbothpigmentandofpiled-up mor- phology, weresuppressed intumorigenicity comparedwith thecontrol cells. Theseeffects wereallreversible. A signifi- cantpercentage ofmiceinjected withBrdU-treated cells wereprotected against subsequent tumorformation when challenged withmalignant control cells. Thedegree ofpro- tection conferred on themicecorrelated wellwiththe numberofvirusparticles countedintheinjected cells. Therewasalsogoodcorrelation betweentheamountof cell-associated virusand thedegreeofsuppression of malignancy forcellstreatedcontinuously with1 Mgof BrdUperml,butnotasgoodforcells treated forshortpe- riods withhigherconcentrations ofBrdU. Reversible suppression oftumorigenic potential ofmouse melanoma cells growninculture forlongperiods inmedium containing lowconcentrations ofthethymidine analog 5- bromodeoxyuridine