The promoting effect of tumour necrosis factor alpha in radiation-induced cell transformation.
The ability of tumour necrosis factor alpha (TNF-alpha), a potent endogenous inflammatory agent, to promote malignant transformation of Syrian hamster embryo cells (SHE) initiated by a 0.5-Gy dose of alpha-particles was investigated. Opsonized zymosan particles, which were phagocytosed by a human macrophage-like cell line, triggered TNF-alpha production from U937 cells. This cell supernatant could significantly increase the transformation frequency (TF) of primary SHE cells previously irradiated by a 0.5-Gy dose of alpha-particles. The TF decreased significantly if monoclonal antibody against TNF-alpha was added to the supernatant. Similarly, recombinant human TNF-alpha (rhTNF-alpha) increased the TF of alpha-irradiated primary SHE cells to an even greater extent. Addition of TNF-alpha to subcultures of irradiated SHE cells permitted the continuous propagation of these primary cells. In contrast, both TNF-alpha-treated control and alpha-irradiated cells without subsequent TNF-alpha treatment senesced after 7-15 passages. Irradiated SHE cells treated continuously with TNF-alpha could be subcultured over 40 passages and produced fibrosarcomas upon inoculation into nude mice. Our results provide the first evidence that TNF-alpha released by activated macrophages may contribute to the process of malignant transformation initiated by low-dose alpha-particles.
Guo
R F
RF
Department of Immunology, Institute of Infectious Disease, Beijing, China.
Gong
Y F
YF
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects; D005354:Fibrosarcoma / Q000473:pathology; D006801:Humans; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha