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. 1978 Aug;38(2):302–309. doi: 10.1038/bjc.1978.202

Tumour-necrosis factor from the rabbit. I. Mode of action, specificity and physicochemical properties.

N Matthews, J F Watkins
PMCID: PMC2009711  PMID: 698046

Abstract

Sera from rabbits injected with BCG and then with endotoxin contain a factor (tumour-necrosis factor TNF) which, even at high dilutions, is cytotoxic in vitro for mouse L cells and some other cell lines. Using a 51Cr-release assay, cytotoxicity was detected as early as 7-8 h after addition of TNF serum to L cells and cell death was evident microscopically by 24 h. TNF was cytotoxic at 37 degrees C but not at 21 degrees C or 4 degrees C, and acted on both dividing and non-dividing cells. The antimetabolites sodium azide and dinitrophenol partially protected L cells from TNF, suggesting that actively metabolizing cells are the most sensitive. Treatment of L cells with trypsin did not delay cytotoxicity nor was cytotoxicity inhibited in the presence of various saccharide derivatives of cell-surface glycoproteins. Rabbit TNF was remarkably stable with a mol. wt. of 40-50,000. It was eluted with the more acidic serum proteins on ion-exchange chromatography, but precipitated in 50%-saturated ammonium sulphate. Sensitivity to TNF could not be correlated with tumourigenicity of several animal and human lines tested nor with the production of C-type viruses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Currie G. A., Basham C. Activated macrophages release a factor which lyses malignant cells but not normal cells. J Exp Med. 1975 Dec 1;142(6):1600–1605. doi: 10.1084/jem.142.6.1600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ferluga J., Schorlemmer H. U., Baptista L. C., Allison A. C. Cytolytic effects of the complement cleavage product, C3a. Br J Cancer. 1976 Dec;34(6):626–634. doi: 10.1038/bjc.1976.223. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Green S., Dobrjansky A., Carswell E. A., Kassel R. L., Old L. J., Fiore N., Schwartz M. K. Partial purification of a serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1976 Feb;73(2):381–385. doi: 10.1073/pnas.73.2.381. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Helson L., Green S., Carswell E., Old L. J. Effect of tumour necrosis factor on cultured human melanoma cells. Nature. 1975 Dec 25;258(5537):731–732. doi: 10.1038/258731a0. [DOI] [PubMed] [Google Scholar]
  6. Herberman R. B., Nunn M. E., Lavrin D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of reactivity and specificity. Int J Cancer. 1975 Aug 15;16(2):216–229. doi: 10.1002/ijc.2910160204. [DOI] [PubMed] [Google Scholar]
  7. Hibbs J. B., Jr Discrimination between neoplastic and non-neoplastic cells in vitro by activated macrophages. J Natl Cancer Inst. 1974 Nov;53(5):1487–1492. doi: 10.1093/jnci/53.5.1487. [DOI] [PubMed] [Google Scholar]
  8. Holtermann O. A., Klein E., Casale G. P. Selective cytotoxicity of peritoneal leucocytes for neoplastic cells. Cell Immunol. 1973 Dec;9(3):339–352. doi: 10.1016/0008-8749(73)90049-x. [DOI] [PubMed] [Google Scholar]
  9. Keller R. Modulation of cell proliferation by macrophages: a possible function apart from cytotoxic tumour rejection. Br J Cancer. 1974 Nov;30(5):401–415. doi: 10.1038/bjc.1974.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. LITTLEFIELD J. W. THREE DEGREES OF GUANYLIC ACID--INOSINIC ACID PYROPHOSPHORYLASE DEFICIENCY IN MOUSE FIBROBLASTS. Nature. 1964 Sep 12;203:1142–1144. doi: 10.1038/2031142a0. [DOI] [PubMed] [Google Scholar]
  11. MACPHERSON I., STOKER M. Polyoma transformation of hamster cell clones--an investigation of genetic factors affecting cell competence. Virology. 1962 Feb;16:147–151. doi: 10.1016/0042-6822(62)90290-8. [DOI] [PubMed] [Google Scholar]
  12. McClelland D. B., Furth R. V. In vitro synthesis of beta1C/beta1A globulin (the C3 component of complement) by tissues and leucocytes of mice. Immunology. 1976 Dec;31(6):855–861. [PMC free article] [PubMed] [Google Scholar]
  13. Old L. J. Tumor necrosis factor. Clin Bull. 1976;6(3):118–120. [PubMed] [Google Scholar]
  14. REYNOLDS E. S. The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol. 1963 Apr;17:208–212. doi: 10.1083/jcb.17.1.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Schorlemmer H. U., Allison A. C. Effects of activated complement components on enzyme secretion by macrophages. Immunology. 1976 Nov;31(5):781–788. [PMC free article] [PubMed] [Google Scholar]
  16. Watkins J. F. Production of hybrid cells by fusion of human malignant tumour cells and primary mouse embryo cells. Int J Cancer. 1977 Oct 15;20(4):535–542. doi: 10.1002/ijc.2910200410. [DOI] [PubMed] [Google Scholar]
  17. Watkins J. F., Sanger C. Properties of a cell line from human adenocarcinoma of the rectum. Br J Cancer. 1977 Jun;35(6):785–794. doi: 10.1038/bjc.1977.120. [DOI] [PMC free article] [PubMed] [Google Scholar]

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