Growth-regulatory control of human cell hybrids in nude mice

The role of natural killer (NK) cells in the control of growth of human cell hybrids in nude mice was evaluated. Both nontumorigenic and tumorigenic HeLa-fibroblast hybrids were highly sensitive to NK-mediated cytotoxicity, but neither hybrid induced such activity when injected into nude mice. Furthermore, tumorigenic hybrids grew in mice which had high levels of NK activity induced by i.p. inoculation of Corynebacterium parvum vaccine. Histological examination of the nontumorigenic and tumorigenic populations inoculated s.c. into nude mice indicated that both populations initially divide actively for the first 3 to 4 days. After this time, the nontumorigenic cells showed a dramatic decline in mitotic activity accompanied by a morphological shift to a more fibroblastoid appearance. The cells remained in the animal as a viable nondividing tissue. The tumorigenic population continued to actively divided and produced a large progressively growing tumor. This series of events determined from histological examination was supported by kinetic studies. These results suggest that NK cells play no role in the suppression of growth of the nontumorigenic hybrid cells and that host-mediated growth-regulatory control is responsible for the shutdown of mitotic activity of these cells without causing their death.