USPHS Grants CA-l2844 and CA-02357 from the National Cancer

Eight sublines ofthe radiation-induced lymphoma S-l033 of C57BL/ 10 (hereafter called BlO) origin were established by exposing the cells in vivo to eight antineoplastic agents for a number of transplant generations. The parental and drug-treated sublines were tested for immunogenic proper ties, i.e., the ability to elicit allograft reactions in the host of origin and in congenic-resistant mice differing for the S-D or K-I-S regions of the H-2 complex. Lymphoma S-1033 and all drug-treated sublines except one were found to be essentially nonimmunogenic for BlO mice. The 5-DIC subline, when exposed for 8 to 12 transplant generations to dimethyltniazenoim idazolecarboxam ide, became imm uno genic for syngeneic BlO mice, asjudged from prolongation of survival time. Large i.v. inocula (l0@ cells) of 5-1033 and of the drug-treated sublines, with the possible exception of the cyclophosphamide-treated and dimethyltniazenoimid azolecarboxamide-treated lymphomas, were more effec tively rejected by K-I-Sthan by S-D-incompatible mice. Dilution escape (i.e., tumor rejection after challenge with large inocula, and lethal tumor growth after injection of small inocula of lymphoma cells in allogeneic recipients) occurred in K-I-S-incompatible mice that were inoculated with 5-1033 and three drug-treated (5-fluorouracil, cyclo phosphamide, and pyrazolcarboxamideamino) sublines. No dilution escape occurred with dimethyltriazenoimid azolecarboxamide or bischloroethylnitrosourea sublines. These data favor the hypothesis that various types of immunogenic changes of neoplastic cells may occur in tumor-bearing hosts following treatment with antineoplastic agents in vivo.