In vitro and in vivo indications of the carcinogenicity and toxicity of food dyes.

Eight food dyes or commercial color mixtures certified for use in the United States were tested for their ability to transform in vitro a serial line of Fischer rat embryo cells previously reported to be a sensitive indicator of chemicals having carcinogenic potential. Malignant cell transformation was induced by a commercial mixture (G2024) of two of these dyes (Blue 1 and Yellow 5) and by Blue 2, Green 3 (one of two experiments) and Red 4. Food dyes Blue 1, Red 3, Yellow 5 and Yellow 6 did not induce cell transformation. One to 1.5 mg of each dye was injected into suckling LVG or Graffi hamsters which were monitored for tumor induction and/or death over a 330-day period. None of the non-transforming dyes (Blue 1, Red 3, Yellow 5, Yellow 6) or Green 3 induced a significant increase in tumor (mostly lymphoma) incidence or animal mortality. Three of the transforming dyes (Blue 2, Green 2024, Red 4) did increase tumor incidence and/or mortality in at least one strain of hamster. We conclude the the in vitro assay suggested that certain food dyes were carcinogens and that in vivo studies in hamsters supported this interpretation.

Suppression of murine type-C RNA virogenes by type-specific oncornavirus vaccines: prospects for prevention of cancer.

Immunization of crossbred and F1 mice with combined killed and live Gross leukemia virus AKR type-C viral vaccines suppressed endogeneous N-type AKR virus up to 10,000-fold for significant periods during early life. Since several previous studies in the same and similar crossbred systems revealed direct correlations between low and high levels of type-C virus early in life with low and high incidences of leukemia and other cancers later in life, we believe that prospects for suppression of spontaneous neoplasms are good; however, 8-14 months will be required to achieve the final results. Should cancers be prevented by serotype-specific vaccines, such evidence would provide conclusive proof of endogenous viral etiology.

Activation and isolation of hamster-specific C-type RNA viruses from tumors induced by cell cultures transformed by chemical carcinogens.

Cell cultures of Syrian hamster embryo were treated for 7 days with selected chemicals. Certain cultures were morphologically transformed by three different chemical preparations and yielded cell lines that subsequently produced malignant tumors in hamsters. Although the cell lines were negative for infectious virus before inoculation into animals, hamster-specific C-type RNA virus was isolated from tumors or from cell lines derived from the tumors. Since infectious C-type viruses are usually not demonstrable in hamster tissues of normal or tumor origin, we conclude that the chemical treatment and activation of the viruses are related events.

Group-specific antigen expression during embryogenesis of the genome of the C-type RNA tumor virus: implications for ontogenesis and oncogenesis.

Tests for the group-specific antigen of the C-type RNA tumor virus showed that mouse embryos of all strains tested, at some stage of development in utero, revealed detectable titers of group-specific antigen in one or more of their tissues; younger, rather than older, embryos were likely to be positive, particularly in those strains which normally reveal little or no expression of the RNA genome postnatally. The antigens were found in embryos of low-leukemia strains, free of infectious virus. These new findings support a previously stated hypothesis that the genome of RNA tumor viruses, mostly switched off for infectious virus expression, is vertically transmitted as part of the natural genetic apparatus of normal mouse cells. Since group-specific antigens have also been described in chick embryos and immunological tolerance to homologous group-specific antigens has been demonstrated in hamsters and cats as well as in mice and chickens, the hypothesis has been extended to include vertebrate cells in general. Finally, the high incidence and titers of the group-specific antigen suggest that the genes for RNA tumor virus, which later in life act as determinants of cancer, may be important also as gene determinants in the developing embryo.

Complement-fixing antigens in hamster tumors induced by the Bryan strain of Rous sarcoma virus.

Hamster tumors transplanted subcutaneously from primary intracranial tumors which developed after inoculation of the Bryan strain of Rous sarcoma virus, contained virusspecific tumor antigens indistinguishable from those induced by the Schmidt-Ruppin strain.