Diversity of the promoting action of cyclosporine on the induction of murine lymphoid tumors.
We have previously demonstrated that cyclosporine (CsA), a powerful immunosuppressant, enhanced the development of thymic lymphomas in Swiss Webster mice initiated with a single subcarcinogenic dose of N-methyl-N-nitrosourea and enhanced the spontaneous development of thymic tumors in AKR mice. In the present study, we examined whether the initiation of mice with a single dose of gamma-radiation modified the target cell specificity of the CsA promotion of lymphoma induction. Male Swiss Webster and C57B/6 mice were divided into four groups. The mice in group 1 and 2 of both strains were given a single dose (350 rad) of gamma-radiation; 10 days thereafter group 1 was given a basal diet and group 2 a basal diet containing 0.015% CsA for 25-35 weeks. Groups 3 and 4 consisted of control mice without radiation and were maintained on a basal or a CsA diet. None of the mice in either strain in groups 1, 3 and 4 developed tumors. Eighteen out of 39 (46%) Swiss Webster mice that received radiation followed by a CsA diet developed tumors involving mesenteric lymph nodes and the spleen. The tumor cells had immunoglobulins on their surface and were negative for Thy 1, suggesting lymphomas of B cell lineage. Four mice (10%) developed thymic tumors which were positive for Thy 1. Seven of 14 (50%) C57B/6 treated with radiation and CsA developed thymic tumors, while none developed tumors of B cell lineage. The results indicate that CsA is a potent promoter of the induction of lymphomas in mice and that the cell type is determined by the type of initiating agents and the strain of mice.
Hattori
A
A
Department of Pathology, University of Pittsburgh School of Medicine, PA 15261.
Kunz
H W
HW
Gill
T J
TJ
Pan
S F
SF
Shinozuka
H
H
D000818:Animals; D002273:Carcinogens; D003524:Cyclosporins / Q000633:toxicity*; D004357:Drug Synergism; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008770:Methylnitrosourea; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D011947:Receptors, Antigen, B-Cell / Q000032:analysis; D013045:Species Specificity; D013953:Thymus Neoplasms / Q000139:chemically induced / Q000473:pathology*
D002273:Carcinogens; D003524:Cyclosporins; D011947:Receptors, Antigen, B-Cell; D008770:Methylnitrosourea