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Low passage Fischer rat embryo cultures, which are normally very resistant to transformation by 3-methyicholanthrene but are highly susceptible when chronically infected with the Rauscher murine leukemia virus, were completely protected from transformation by methylcholanthrene when treated with neutralizing antiby specific for the leukemia virus prior to and during treatment with methylcholanthrene. Sister cultures were not protected by neutralizing antibody specific for the B-tropic radiation leukemia virus. This demonstrates clearly a definite type specific role for Rauscher murine leukemia virus in the 3-methylcholanthrene transformation system in rat cells. We have previously described a Fischer rat embryo cell line that at a low passage level (<60) requires either the addition of an exogenous type-C RNA virus or treatment with an halogenated pyrimidine prior to treatment with a chemical carcinogen in order for transformation to occur (1, 2). At passage levels higher than 60, chemicals known to be carcinogenic in animals do on occasion transform the cells without preinfection by type-C RNA virus. These high passage cells appear to be negative for infectious type-C RNA virus; however, the gs-1 antigen of RaLV (the endogenous type-C RNA rat virus) is often expressed after transformation (2), and the rat type-C virus can be induced in both the low and high passage cells by 5-iodo-2'-deoxyuridine (I. Shif, personal communication). We have recently shown that two agents that inhibit this induction by iododeoxyuridine, namely, streptonigrin (3) and cordycepin (4), protect the rat cells from transformation by the polycyclic hydrocarbon 3-methylcholanthrene. We report here that low passage Fischer rat embryo cultures chronically infected with the Rauscher murine leukemia virus (RLV) are protected from transformation by 3-methylcholanthrene if treated with neutralizing antibody specific for RLV; the cultures were not protected by neutralizing antibody specific for the B-tropic radiation leukemia virus (RadLV) (5), which is Gross-like in its neutralizing antigenic determinants. MATERIALS AND METHODSReduction in plating efficiency of the chronically infected Fischer rat embryo cells relative to a control serum was used to determine the toxicity of the antisera. Five hundred cells in 5 ml of complete growth medium (Eagle's minimal essential medium in Earle's salts supplemented with 5% dialyzed calf serum, 5% fetal bovine serum, 2 mM L-glutamine, 0.1 mM nonessential amino acids, and a mixture of 100 units of penicillin and 100 ,tg of streptomycin per ml) were added to each 60-mm plastic dish (Lux). After a 4-hr incubation period at 370 (to allow cell attachment) the medium was decanted and replaced with a fresh medium now containing serial, 2-fold dilutions of antisera or control serum. Five days later the cells were fixed and stained (Giemsa)

Fischer rat embryo cells chronically infected with Rauscher murine leukemia virus, and known to be sensitive to transformation by potent chemical carcinogens, were transformed by the weak carcinogen 4-nitropyridine-1-oxide. Transformed cells grew in semi-solid agar and produced tumors in newborn Fischer rats. Transformation was inhibited by antisera specific for the ecotropic Rauscher murine leukemia virus, but not by antisera of equal toxicity specific for xenotropic Swiss mouse AT-124 virus.