Growth Inhibition of Normal or Drug-Treated Lymphoma Cells in Lethally Irradiated Mice2

Abstract

Radioresistant inhibition of tumors (RIT), i.e., impairment of the growth of tumor cells inoculated into lethally irradiated mice, was studied in allogeneic or hybrid mice challenged with LSTRA or L5178Y lymphoma cells carrying the H-2^d haplotype. The studies were conducted also with LSTRA/DTIC, L5178Y/DTIC, and L5178Y/DTIC/Ara sublines, antigenically altered after treatment in vivo with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole- 4-carboxamide (DTIC). The extent of RIT responses was evaluated by measurement of tumor cell proliferation in the spleens and livers of lethally irradiated recipient mice by use of the ¹²⁵I-labeled 2′-deoxyuridine uptake method. Lymphoma cells were inoculated into histocompatible recipients or into allogeneic mice, either susceptible or resistant to H-2^d bone marrow graft, according to the hematopoietic-histocompatibility (Hh) system. RIT responses were detected against both parental and DTIC-treated sublines in Hh-resistant or Hh-susceptible allogeneic hosts. Marginal or no RIT responses against H-2^d LSTRA or L5178Y lymphomas were found in inbred or hybrid hosts carrying the H-2^d haplotype. Nevertheless, weak but significant responses were detected in recipients of the same genotype challenged with DTIC sublines. The results of the experiments suggested that: a) parental or DTIC-treated lymphomas could share Hh antigens with normal bone marrow cells of the strain of origin though no direct evidence was obtained in these studies; b) leukemia cells might express tumor-associated antigens, not detectable in normal bone marrow cells, that are capable of eliciting RIT responses in Hh-susceptible allogeneic mice; and c) additional transplantation antigens could be expressed by DTIC sublines that elicited presumably weak RIT responses in lethally irradiated histocompatible recipient hosts.