Transplantation resistance of drug-treated hybrid or allogeneic mice against murine lymphomas. I. Immunopharmacology studies.
Sequential treatment of mice with non-lethal doses of 5(3,3'-dimethyl-l-triazeno)-imidazole-4-carboxamide (DTIC) and cyclophosphamide (Cy) was found to produce long-term inhibition of endogenous cell proliferation in the spleen and profound impairment of classical allograft responses, similar to that detectable in lethally irradiated mice. Studies were carried out with drug-treated (i.e. treated with DTIC + Cy) conventional or nude mice inoculated with lymphoma cells homozygous for the H-2b or H-2d haplotype. Transplantation resistance in various tumour-host combinations was studied in terms of survival times after tumor challenge or lymphoma cell proliferation in spleen and liver, measured by the uptake of DNA precursor 125I-labelled 5-iodo-2'-deoxyuridine ([125I]dUrd). The results of in vivo transplantation immunity tests or in vitro tests of generation of cytotoxic lymphocytes confirmed that classical T-dependent allograft responses were abrogated by drug treatment of H-2-incompatible hosts. However, localized resistance against lymphoma graft, mainly at spleen level, was found in drug-treated hybrid mice, or conventional and "nude" allogeneic recipients, as judged by [123I]dUrd uptake inhibition. Resistance presumably regulated, at least in part by the Hh (hemopoietic histocompatibility) system, was abrogated by pretreatment with carrageenan, an antimacrophage agent. In addition, treatment with DTIC + Cy did not abrogate NK activity of mice when the in vitro cytotoxicity test was conducted 5 h after Cy administration, i.e. at the time used for tumor challenge in vivo. It was concluded that selected immunological functions (i.e., antilymphoma natural resistance insensitive to DTIC + Cy, called drug-resistant inhibition of tumors, DRIT) possibly of non-T origin, similar to those detectable in lethally-irradiated mice, can be retained by hosts subjected to high doses of certain anti-tumor agents.
D000818:Animals; D001854:Bone Marrow Cells; D002351:Carrageenan / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology*; D003606:Dacarbazine / Q000494:pharmacology*; D005260:Female; D007694:Killer Cells, Natural / Q000276:immunology; D008099:Liver / Q000166:cytology; D008223:Lymphoma / Q000276:immunology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D014181:Transplantation Immunology / Q000187:drug effects*
D003606:Dacarbazine; D003520:Cyclophosphamide; D002351:Carrageenan