Natural resistance of mice pretreated with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) + cyclophosphamide (Cy) against virus-induced lymphoma cells.

Virus-induced leukemia was inoculated into histocompatible or allogeneic hosts pretreated with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) + Cyclophosphamide (Cy), which abrogate endogenous cell proliferation and T-dependent graft responses, but not selected "natural resistance" (NR) activities. Marked impairment of lymphoma cell growth occurred mainly in the spleen of allogeneic mice with respect to that of histocompatible controls. Tumor inhibition was still present when lymphoma challenge was performed on day + 3 after Cy administration. Parallel studies on "natural killer" (NK) activity in vitro or in vivo showed that complete abrogation of the NK function was detectable on day + 3 or + 6 after Cy treatment. It was concluded that in vivo inhibition of lymphoma growth in mice pretreated with DTIC + Cy could be a drug-resistant NR at least in part distinguishable from the NK function.