Thymic T-cell lymphoma with the CD8+ (OX-8), CD4+ (W3/25) phenotype, induced in F344/NCr rats by nitroso-2-hydroxypropylurea

Abstract

Thymic T-cell lymphomas were induced by administration of nitroso-2-hydroxypropylurea (NHPU) at a dose of 1.6 mg by gavage twice weekly for each of 20 weeks in F344/NCr rats. Lymphomas began to appear 5-10 weeks after the first intubation. Primary and transplantable tumors were subjected to morphological, histogenetic and immunological characterization. Lymphomas composed of medium-sized lymphocytes (prolymphocytes) arose within individual thymic lobules, often in atrophic thymic lobes and metastasized slowly to the T-cell zones of the splenic white pulp. The tissue fixative was important for tumor morphology and classification, with Bouin's fluid markedly superior to formalin. Transplantable tumors were similar morphologically except for one lymphoblastic lymphoma, but all transplants metastasized quickly to spleen, liver, thymus, and other tissues. Fluorescence-activated cell sorter (FACS) analysis of primary and transplantable lymphomas revealed cells of the T-cell lineage, with tumor cells expressing both OX-8 (CD8) and W3/25 (CD4) antigens. Immunoperoxidase studies of spleen showed infiltration of OX-8+ tumor cells first into T-cell dependent areas of the splenic white pulp.