Abstract
Genetically anemic SI/SI(d) mice have been shown previously to have a defective hematopoietic environment which prevents extensive erythroid differentiation of normal hematopoietic stem cells and also confers resistance to the erythroleukemia-inducing virus, Friend spleen focus-forming virus (SFFV). In this study, we show that the relative resistance of SI/SI(d) mice to transformation by SFFV is not due to the inability of SFFV to replicate, nor is it because SFFV cannot transform erythroid cells, in the spleens of these mice. Injection of syngeneic +/+ mouse spleen cells, previously infected in vivo with SFFV, into secondary SI/SI(d) recipients resulted in marked splenic enlargement, and the appearance of large numbers of erythropoietin (Epo)-independent erythroid colonies in plasma clot culture. The cellular proliferation observed in these SI/SI(d) secondary recipients appeared to be due to infection and transformation of host SI/SI(d) cells rather than the growth of possible tumor colony-forming units (TCFU) present in the infected +/+ spleens, because preirradiation of the SI/SI(d) recipients abolished the splenomegaly and appearance of Epo- independent erythroid colonies. Furthermore, prior irradiation (1,200 rads) of donor spleen cells from SFFV-infected +/+ mice only slightly reduced spleen focus formation in unirradiated SI/SI(d) recipients. The conclusion that SI/SI(d) target cells could be infected and transformed by SFFV was confirmed directly by injecting a high titered preparation of SFFV into SI/SI(d) mice. SI/SI(d) mice were not absolutely resistant to infection or transformation by SFFV. Nevertheless, cells from the spleens of SFFV-infected mice were unable to form tumor colonies (TCFU) in irradiated SI/SI(d) recipients, suggesting that TCFU are either present at an undetectably low frequency in these spleens, or that they are still subject to the regulatory influences of the Steel locus.
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Selected References
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- AXELRAD A. A., STEEVES R. A. ASSAY FOR FRIEND LEUKEMIA VIRUS: RAPID QUANTITATIVE METHOD BASED ON ENUMERATION OF MACROSCOPIC SPLEEN FOCI IN MICE. Virology. 1964 Nov;24:513–518. doi: 10.1016/0042-6822(64)90199-0. [DOI] [PubMed] [Google Scholar]
- Adamson J. W. The erythropoietin-hematocrit relationship in normal and polycythemic man: implications of marrow regulation. Blood. 1968 Oct;32(4):597–609. [PubMed] [Google Scholar]
- Bennett M., Steeves R. A., Cudkowicz G., Mirand E. A., Russell L. B. Mutant Sl alleles of mice affect susceptibility to Friend spleen focus-forming virus. Science. 1968 Nov 1;162(3853):564–565. doi: 10.1126/science.162.3853.564. [DOI] [PubMed] [Google Scholar]
- Bernstein A., Mak T. W., Stephenson J. R. The Friend virus genome: evidence for the stable association of MuLV sequences and sequences involved in erythroleukemic transformation. Cell. 1977 Sep;12(1):287–294. doi: 10.1016/0092-8674(77)90206-9. [DOI] [PubMed] [Google Scholar]
- Bernstein S. E. Tissue transplantation as an analytic and therapeutic tool in hereditary anemias. Am J Surg. 1970 Apr;119(4):448–451. doi: 10.1016/0002-9610(70)90148-0. [DOI] [PubMed] [Google Scholar]
- Chui D. H., Loyer B. V. Erythropoiesis in steel mutant mice: effects of erythropoietin in vitro. Blood. 1975 Mar;45(3):427–433. [PubMed] [Google Scholar]
- Clarke B. J., Axelrad A. A., Housman D. Friend spleen focus-forming virus production in vitro by a nonerythroid cell line. J Natl Cancer Inst. 1976 Oct;57(4):853–859. doi: 10.1093/jnci/57.4.853. [DOI] [PubMed] [Google Scholar]
- Eckner R. J. Continuous replication of Friend virus complex (spleen focus-forming virus-lymphatic leukemia-inducing virus) in mouse embryo fibroblasts. Retention of leukemogenicity and loss of immunosuppressive properties. J Exp Med. 1975 Oct 1;142(4):936–948. doi: 10.1084/jem.142.4.936. [DOI] [PMC free article] [PubMed] [Google Scholar]
- FRIEND C., HADDAD J. R. Tumor formation with transplants of spleen or liver from mice with virus-induced leukemia. J Natl Cancer Inst. 1960 Dec;25:1279–1285. [PubMed] [Google Scholar]
- Freedman H. A., Lilly F. Properties of cell lines derived from tumors induced by Friend virus in BALB/c and BALB/c-H-2b mice. J Exp Med. 1975 Jul 1;142(1):212–223. doi: 10.1084/jem.142.1.212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrison D. E., Russell E. S. The response of W-W v and Sl-Sl d anaemic mice to haemopoietic stimuli. Br J Haematol. 1972 Feb;22(2):155–168. doi: 10.1111/j.1365-2141.1972.tb08797.x. [DOI] [PubMed] [Google Scholar]
- Horoszewicz J. S., Leong S. S., Carter W. A. Friend leukemia: rapid development of erythropoietin-independent hematopoietic precursors. J Natl Cancer Inst. 1975 Jan;54(1):265–267. doi: 10.1093/jnci/54.1.265. [DOI] [PubMed] [Google Scholar]
- Johnson G. R., Metcalf D. Pure and mixed erythroid colony formation in vitro stimulated by spleen conditioned medium with no detectable erythropoietin. Proc Natl Acad Sci U S A. 1977 Sep;74(9):3879–3882. doi: 10.1073/pnas.74.9.3879. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liao S. K., Axelrad A. A. Erythropoietin-independent erythroid colony formation in vitro by hemopoietic cells of mice infected with friend virus. Int J Cancer. 1975 Mar 15;15(3):467–482. doi: 10.1002/ijc.2910150313. [DOI] [PubMed] [Google Scholar]
- McCulloch E. A., Siminovitch L., Till J. E., Russell E. S., Bernstein S. E. The cellular basis of the genetically determined hemopoietic defect in anemic mice of genotype Sl-Sld. Blood. 1965 Oct;26(4):399–410. [PubMed] [Google Scholar]
- McLeod D. L., Shreeve M. M., Axelrad A. A. Improved plasma culture system for production of erythrocytic colonies in vitro: quantitative assay method for CFU-E. Blood. 1974 Oct;44(4):517–534. [PubMed] [Google Scholar]
- Mirand E. A., Steeves R. A., Lange R. D., Grace J. T., Jr Virus-induced polycythemia in mice: erythropoiesis without erythropoietin. Proc Soc Exp Biol Med. 1968 Jul;128(3):844–849. doi: 10.3181/00379727-128-33139. [DOI] [PubMed] [Google Scholar]
- Prchal J. F., Axelrad A. A. Letter: Bone-marrow responses in polycythemia vera. N Engl J Med. 1974 Jun 13;290(24):1382–1382. doi: 10.1056/nejm197406132902419. [DOI] [PubMed] [Google Scholar]
- Sassa S., Takaku F., Nakao K. Regulation of erythropoiesis in the Friend leukemia mouse. Blood. 1968 Jun;31(6):758–765. [PubMed] [Google Scholar]
- Steeves R. A., Bubbers J. E., Plata F., Lilly F. Origin of spleen colonies generated by Friend virus-infected cells in mice. Cancer Res. 1978 Sep;38(9):2729–2733. [PubMed] [Google Scholar]
- Steeves R. A., Mirand E. A., Thomson S., Avila L. Enhancement of spleen focus formation and virus replication in Friend virus-infected mice. Cancer Res. 1969 May;29(5):1111–1116. [PubMed] [Google Scholar]
- Sutherland D. J., Till J. E., McCulloch E. A. A kinetic study of the genetic control of hemopoietic progenitor cells assayed in culture and in vivo. J Cell Physiol. 1970 Jun;75(3):267–274. doi: 10.1002/jcp.1040750302. [DOI] [PubMed] [Google Scholar]
- Tambourin P., Wendling F. Malignant transformation and erythroid differentiation by polycythaemia-inducing Friend virus. Nat New Biol. 1971 Dec 22;234(51):230–233. doi: 10.1038/newbio234230a0. [DOI] [PubMed] [Google Scholar]
- Wendling F., Tambourin P. E. Oncogenicity of Friend-virus-infected cells: determination of origin of spleen colonies by the H-2 antigens as genetic markers. Int J Cancer. 1978 Oct 15;22(4):479–486. doi: 10.1002/ijc.2910220418. [DOI] [PubMed] [Google Scholar]