The presence of adenovirus-specific antigens in hamster cells rendered neoplastic by adenovirus 1-SV40 and adenovirus 2-SV40 hybrid viruses.

Extensive studies concerning the oncogenicity of human adenoviruses (Ad.) in newborn hamsters have demonstrated a lack of oneogenic potential in the strains of Ad. 1, 2, and 5 tested thus far. Such studies have resulted in the classification of these serotypes in the nononcogenic subgroup (group C) which differs from the mildly oncogenic subgroup (group B) (including Ad. 3, 7, 14, 16, and 21) and the highly oncogenic subgroup (group A) (including Ad. 12, 18, and 31) with respect to the guanine plus cytosine (G-C) content of the viral DNA, oncogenic potential for hamsters, and hemagglutination characteristics.' Studies of T antigens have demonstrated that virus-free cells rendered neoplastic by oncogenic adenoviruses as well as Simian virus 40 (SV 40) and polyoma viruses contain specific viral genetic determinants which are integrated within these neoplastic cells.2-4 By "integration" we mean that viral genetic determinants have be come heritable cell factors. In addition, studies of hybrid-virus populations obtained by mixed infection of monkey kidney cells with SV40 and oncogenic adenoviruses types 7 and 12 demonstrated marked oncogenicity and ability to transform cells in vitro, and suggested the integration in the tumor and transformed cells of both SV40 and adenovirus genetic material.' We have recently found that the "hybrid" virus populations obtained by growing nononcogenic Ad. 1, 2, and 5 with SV40 are likewise capable of inducing tumors in hamsters in vivo,' and that the Ad. 2 hybrid produces transformation of hamster cells in vitro.7 These tumors and transformed cells provided an approach to the question of whether genetic material from nononcogenic adenoviruses could be integrated into neoplastic cells. This report describes studies utilizing serologic markers to show that both SV40 and adenovirus genetic material are integrated in tumor and transformed cells induced by populations of nononcogenic adenoviruses which are hybrids with SV40. Materials and Methods.-Tumor and transformed cell lines: Three lines of cells were studied. The Ad. 1++8 hybrid virus strain previously described was inoculated into newborn hamsters. A tumor which developed 142 days later was carried through two transplant generations in newborn hamsters and thereafter as a cell line in tissue culture; the cell line is referred to here as Ad. 1 ++ TL-1. The Ad. 2++ HK-1 and HK-2 cell lines,7 were obtained by transforming weanling hamster kidney (WHK) cells in vitro with the Ad. 2++ hybrid virus population.'0 The derivation of these lines and the characteristics of the tumors produced on transplantation to hamsters have been described.7 11 The three cell lines, both as tumor and tissue culture cells, were repeatedly tested for virus. Culture fluids and 10% extracts of tissue culture cells and tumors were inoculated into human embryonic kidney (HEK) and African green monkey kidney (AGMK) cell cultures, with blind passage at 3-4 weeks; in 20 such tests no adenovirus was ever isolated, but two Ad. 2++ tumor extracts yielded small aunouuuts of SV40.7 In addition, viable tumor or tissue culture cells were