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The enhancement or delay in the appearance of spontaneous reticulum cell neoplasms (RCN-B) in SJL/J mice was tested. Immunosuppressive treatment with antithymocyte serum and prolonged antigenic stimulation by repeated injections of sheep erythrocytes, leukemogenic cell-free centrifugates, and multichain synthetic polypeptides had no effect on the incidence or latency of spontaneous tumor appearance. Treatment with mineral oil or incomplete Freund adjuvant markedly enhanced tumor appearance (though the abundance of plasma cells induced by these treatments did not evoke the development of plasmacytomas, nor did it affect the incidence of serum paraproteinemia among mice with spontaneous tumors). Treatment with cortisone acetate, however, markedly retarded spontaneous tumor development. Tumors occurring early due to mineral oil and adjuvant treatment all had the characteristics of "RCN-B plasma cell type," and tumors occurring late due to cortisone treatment were all of the "RCN-B reticulum cell type." The possible involvement of the stem cell pool size in the enhancement or delay of spontaneous tumor development was discussed.

The effects of splenectomy on carcinogenesis by a single 10-mg dose of 7,12-dimethylbenz[alpha]anthracene (DMBA) given in olive oil by gavage was tested on BTOs, C57BL/60s, C3H/HeOs, and BALB/cOs mice. The splenectomy, performed a week before the DMBA was given, did not affect physical status or the incidence of acute toxic death of animals. DMBA-treated animals developed neoplasms at a significantly higher rate than did untreated mice. Splenectomy did not influence the overall incidence of neoplasms. Observed tumors in DMBA-treated groups were those of skin, forestomach, colon, liver, lung, adrenal, ovary, breast, hematopoietic-lymphoreticular system, and vascular system, depending on the strain. Types of DMBA-treated neoplasms were affected by prior splenectomy, depending on the strain: Splenectomy inhibited lung adenomas in BALB/cOs females and hepatomas in C57BL/60s females; splenectomy enhanced skin neoplasms in C57BL/60s and squamous cell carcinoma of the forestomach in BTOs males. The most significant change was in the incidence of the group of lymphomas. Myelogenous leukemia was increased in DMBA-treated groups of all strains, but splenectomy inhibited the development of this type of lymphoma.

Inbred strains BALB/c and CBA and noninbred Swiss mice were used for transplanting skin autografts exposed before transplantation for approximately 48 h to (a) culturing in room air and (b) culturing in 45--48% CO2 in air. These pre-transplantation manipulations of skin autografts led to malignant lymphomas in the hosts. The lymphoma incidence was highest in the recipients of the CO2 -treated grafts; moreover, it was greater than the spontaneous incidence even in the recipients of grafts exposed to culturing in air alone, in some types of mice. The following abnormalities of the reticuloendothelial system were noted: (1) proliferation of lymph follicles into irregular masses of pleomorphic cells, (2) hyperplasia with concomitant atrophy of the lymphoid tissue (o) replacement of the lymph follicles by malignant lymphoid cells. Renal lesions resembling membranes glomerulitis occurred occasionally. The occurrence varied in different strains.

The response of lymphoreticular tissues to a single i.p. injection of benzo(a)pyrene was studied in the first generation of C57BL/6J X C3HeB/FeJ F1 and C3HeB/FeJ X A/J F1 mice. Groups of 1-, 15-, and 42-day-old animals of both sexes received 75 or 150 mug of the carcinogen per g body weight. After a period of approximately 90 weeks, a high incidence (up to 43%) of reticulum cell sarcomas was observed in C57BL/6J X C3HeB/FeJ F1 mice treated with benzo(a)pyrene at 40 days of age. Animals treated with carcinogen at younger ages had a lower incidence of reticulum cell sarcomas. These sarcomas showed marked cellular pleomorphism and were classified into histiocytic, epitheloid-nodular, reticulocytic, and fibrocytic forms according to the predominant cell type. Lymphomas of thymic and extrathymic lymphoid origin and leukemia of granulocytic type were seen in a descending order of frequency. Control animals of either strain that were killed at 90 weeks of age were basically free of lymphoreticular tumors, while those kept under observation up to 170 weeks developed these tumors in 24% (C57BL X C3H F1) and 10% (C3H X A/J F1), respectively. Studies revealed that the augmentation and/or acceleration of development of the lymphoreticular neoplasms and specifically reticulum cell sarcomas by benzo(a)pyrene was dependent upon the strain and sex of mice used and the age at which the animals were exposed to carcinogen.

Three patients with multiple myeloma who developed a plasma cell sarcoma during apparently successful chemothapy are described. It is postulated that the chemotherapy induced the sarcomatous change.