Prevention of viral-chemical co-carcinogenesis in vitro by type-specific anti-viral antibody.

Abstract

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)

Chemical‐viral co‐carcinogenesis: Requirement for leukemia virus expression in accelerated transformation

“…The essential nature of leukemia virus infection in cocarcinogenesis was indicated by the failure of the virus to transform the cells when added after chemical treatment (Price et al, 1973). Furthermore, it has been demonstrated that cordycepin and typespecific anti-RLV antisera also inhibit co-carcinogenesis (Price et al, 1975(Price et al, , 1976. However, relatively little systematic experimentation has been performed to elucidate the specific role of viral components in this system.…”

Prevention of spontaneous leukemia in AKR mice by type-specific immunosuppression of endogenous ecotropic virogenes.

“…Price and his associates (21) recently reported the prevention of carcinogen-induced malignant transformation of rat cells in vitro with the use of specific antiviral IgG prior to treatment with carcinogenic chemicals. This and other successful experiments in which Price and his associates employed both typespecific and heterotypic viral neutralizing antisera for suppression of both virus and transformation provided definitive evidence for the existence of virus specific determinants for transformation, because only type-specific antibodies against virus prevented transformation.…”

Chemical enhancement of survival in aggregation of retrovirus‐infected rat cells: An interlaboratory comparison

“…Therefore, RIFRE cells detect a carcinogen-induced early event, survival in aggregation, that eventually progresses to neoplastic transformation. These data also confirm the results of carcinogen-induced transformation of RIFRE cells by others using more traditional methodology [Freeman et al, 1973b[Freeman et al, , 1975Price et al, 1971;Traul et al, 1981al. Previous studies have shown that nontransforming retroviruses play a significant and specific role in promoting the expression of transformation [Freeman et al, 1973a,c;Price et al, 1972aPrice et al, , 1976Price et al, , 1977Fisher and Weinstein, 19801. Low population doublings of Fischer rat embryo cell cultures were resistant to spontaneous transformation, chemically induced transformation, or transformation by murine retroviruses [Price et al, 1972a;Price and Mishra, 19801; cultures chronically infected with retrovirus had an increased sensitivity to transformation by chemical carcinogens.…”