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Although tumors induced in hamsters by adenovirus types 12 In contrast to human CF antibody responses to adenovirus infections, in which the antibody is primarily formed against the group reactive "A"3 or "L"4 soluble antigen, the antibodies in the tumorous hamsters are essentially type-specific and are presumably reactive with antigens similar to the "C'3 or "E"'4 soluble antigens. Thus, sera from hamsters with tumors induced by type 12 react in high titer with type 12 tissue culture antigen, are somewhat less reactive with type 18 antigen, and give no reaction with the other 26 human adenovirus types. Virus-neutralizing antibodies also develop in hamsters with primary and transplanted tumors, but only in those with highest levels of CF antibody." 2 This report describes the direct demonstration of virus-specific CF antigens in the noninfectious or "virus-free" hamster tumors induced by adenovirus types 12 and 18, as well as in transplanted tumors5 and tissue culture cell lines derived therefrom. Also, we describe the induction of tumors in rats by type 12, with comparable findings of noninfectious virus-specific antigens and antibodies in the tumorous animals. Preliminary information on specific CF antigens in hamster tumors induced by SV40 and Rous viruses is also presented.Materials and Methods.-Liter pools of prototype 12 (Huie strain) and 18 (D. C. strain) adenoviruses grown in KB cells, vialed in 1.0 ml quantities, and frozen at -60'C, were used for most experiments in hamsters and rats, and as antigen for neutralization and complement-fixation tests.

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.

When newborn hamsters were inoculated subcutaneously with chicken-embryo lethal orphan virus, tumors developed at the site of inoculation in 23 out of 69 hamsters within 88 to 195 days of inoculation. These tumors and tissue cultures, prepared from a primary tumor, were transplantable to newborn and weanling hamsters. The primary tumors and tissue cultures of a primary tumor were free of demonstrable infectious virus. The virus is the first "nonhuman" adenovirus found to induce tumors in hamsters.