title: The effect of recombinant human tumour necrosis factor on growth and macromolecular synthesis of human epithelial cells.
abstract: We have studied the effect of recombinant human tumour necrosis factor (rHuTNF) on growth and macromolecular synthesis in a range of normal and transformed epithelial cell types. Tumour necrosis factor did not affect the growth of normal human mammary epithelial cells, but its growth-inhibitory action on the SV40-transformed human mammary epithelial cell line HBL-100 increased with passage number in association with a progression of malignant phenotype. However, of two lines derived from nude mouse tumours of HBL-100 lines, one, HBLT-12, did not respond to rHuTNF, and the other, HBLT-11 showed some growth stimulation by high dose rHuTNF. Macromolecular synthesis in HBLT-11 was not affected by rHuTNF. The breast cancer cell lines MCF-7 and BT20 were sensitive to the cytotoxic effects of rHuTNF. In MCF-7 a gradual decrease in RNA and DNA synthesis occurred over 48 h, ending with an accumulation of cells in S and G2 phase of the cell cycle and cell death. The addition of alpha- or gamma-interferon increased, but did not accelerate the cytotoxicity of rHuTNF.
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D009696:Nucleic Acids / Q000096:biosynthesis; D014176:Protein Biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha
chemical_list: D006023:Glycoproteins; D007370:Interferon Type I; D009696:Nucleic Acids; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma