Recent studies demonstrate a correlation between the level of resistance to lysis by natural killer cells and activated macrophages (effector cells) among Syrian hamster cells transformed (tf) by adenovirus (Ad) 2, Ad12, and simian virus 40 (SV40) and the cell lines' tumor inducing capacities. The expression of Ad2 early gene products in somatic cell hybrids was associated with increased susceptibility to effector cells and decreased tumorigenicity. The correlation between viral oncogenicity and the susceptibility or resistance of infected and tf cells to destruction by effector cells, as assayed by release of radiolabel, will be evaluated by comparing the effects of different Ad serotypes and SV40 on cells from different species in which differences in permissiveness of viral replication and tumorigenicity have been observed. The regulation of cytolytic susceptibility during infection and tf of hamster cells will be examined using Ad host range, deletion and temperature sensitive mutants with defined genetic defects in the five early transcriptional regions of the viral genome and by introducing specific viral gene segments into cytolytic resistant cells prior to assaying lysis by effector cells. Using information obtained from the study of the induction of cytolytic susceptibility by nononcogenic Ad encoded polypeptides, approaches will be developed to study the cytolytic resistance observed in cells infected and tf by highly oncogenic DNA viruses. Somatic cell hybridization, coinfection, and infection with selected and constructed hybrid viruses will be used to determine whether there is an active role for early gene products of highly oncogenic viruses in the induction of cytolytic resistance. Monoclonal antibodies will be used to define target cell surface structural differences between cytolytic susceptible and cytolytic resistant cells. Tf cell response to effector cell induced injury will be correlated with tumor inducing capacity in a spectrum of hosts. The ability to contrast molecular mechanisms regulating the level of cellular cytolytic susceptibility during the establishment of neoplastic tf may lead to a better understanding of reasons for the progression of incipient malignancies confronted with the early cellular immune defenses of the host.
