The difficulties of trying to evaluate the complexities of those cell-host interactions that result in either success or failure of sustained tumor growth interferes with a better understanding of viral carcinogenesis. The tumorigenic phenotypes expressed by DNA virus transformed cells represent the end product of those oncogene controlled events that are involved in cell transformation. Differences in these phenotypes provide a window for observing viral oncogene functions. By studying tumor cell dose-tumor incidence relationships and including the time of tumor appearance, we have developed a standard, quantal format for modeling viral transformation and analyzing oncogene-determined tumorigenic phenotypes. The high oncogenicity of certain tumor cells, including adenovirus 12 induced tumor cells, has been related to their expression of low levels of class I MHC proteins. We have used our quantal format to study Adl2 transformed BALB/c mouse cells that express low or high (subsequent to syngeneic class I gene transfection) class I MHC protein levels. Low expressor cells are highly immunogenic in CTL mediated assays of virus-specific immunogenicity and are rejected as allografts by H-2 incompatible mice. High class I expressors are also immunogenic and are quantally more tumorigenic than their low expressor parents. Thus, high oncogenicity of BALB/c mouse cells does not depend on expression of class I MHC proteins. An Ad2/Ad5 ElA ongene-controlled pathway that leads to heightened susceptibility to killing by NK cells exists in Ad2/Ad5 infected and transformed cells. Such a pathway may exist in highly aggressive tumor cells. Evidence for such a pathway was obtained by showing that expression of Ad5 oncogene in sarcoma cells eliminates their tumor inducing capacity by activating their susceptibility to NK cell killing.
