ABSTRACT
This study analyses the production of tumour necrosis factor (TNF)alpha and soluble TNF receptor (sTNF-R) before and after exposure to gamma irradiation and interferon gamma (IFN gamma) in 12 cell lines derived from Ewing's sarcoma (ES)/peripheral primitive neuroectodermal tumours (pPNET). Supernatants from ES/pPNET cell cultures were tested in a TNF alpha-specific amplified enzyme-linked immunosorbent assay (ELISA), a bioassay, and sTNF-Rp55 and sTNF-Rp75 ELISA. The tumour cell lines released minimal amounts of TNF alpha, prominent amounts of sTNF-Rp55 (7/12 cell lines) and no sTNF-Rp75. Exposure to gamma irradiation (5 Gy) either induced (3/12) cell lines) or up-regulated (3/12 cell lines) TNF alpha release without changing sTNF-Rp55 and sTNF-Rp75 levels. Priming of cultures with recombinant human IFN gamma (rhIFN gamma) markedly enhanced TNF alpha secretion in the radiation-responsive cell lines and had no influence on sTNF-Rp55 and sTNF-Rp75 levels. rhIFN gamma affected the magnitude rather than the sensitivity of the radiation response. The TNF alpha secreted was bioactive, as shown by its cytotoxic effect of WEHI-164 cells, and neutralization of its activity by anti-TNF alpha monoclonal antibody. Herbimycin A (a tyrosine-specific protein kinase inhibitor) but not calphostin C (a protein kinase C inhibitor), H89 (a protein kinase A inhibitor), AA-COCF3 (a specific inhibitor of phospholipase A2) and MK-886 (a specific inhibitor of 5-lipoxygenase) abrogated gamma-irradiation-stimulated TNF alpha release. The antioxidants N-acetylcysteine, nordihydroguaiaretic acid and mepacrine dose-dependently inhibited gamma-irradiation-mediated TNF alpha production. Collectively our findings indicate that IFN gamma priming potentiates the secretion of bioactive TNF alpha by ES/pPNET cells in response to gamma irradiation without affecting sTNF-R release. The data suggest a requirement for protein tyrosine kinase activity and a role for reactive oxygen species in the gamma-irradiation-mediated intracellular signalling pathway leading to TNF alpha production.
Subject(s)
Antineoplastic Agents/therapeutic use , Bone Neoplasms/metabolism , Gamma Rays , Interferon-gamma/therapeutic use , Neuroectodermal Tumors/metabolism , Peripheral Nervous System Neoplasms/metabolism , Receptors, Tumor Necrosis Factor/metabolism , Sarcoma, Ewing/metabolism , Tumor Necrosis Factor-alpha/metabolism , Antioxidants/pharmacology , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Gene Expression Regulation, Neoplastic/drug effects , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Neuroectodermal Tumors/drug therapy , Neuroectodermal Tumors/radiotherapy , Peripheral Nervous System Neoplasms/drug therapy , Peripheral Nervous System Neoplasms/radiotherapy , Radiotherapy, Adjuvant/methods , Sarcoma, Ewing/drug therapy , Sarcoma, Ewing/radiotherapy , Tumor Cells, CulturedABSTRACT
Resin tapping involves a high physical workload. We found the mean working-energy expenditure to be 21 +/- 5 kJ min-1. The mean heart-rate amounted to 127 +/- 18 beats min-1. It is the upper extremities where the work-related strain is particularly high. The clinical, function-diagnostic and X-ray examinations (X-ray only for resin tappers) covered 110 resin tappers and a control group of the same size (for pair-matching purposes). The main finding of the examinations was that both the pain and the degree of elbow-joint arthrosis deformans significantly increase in the course of the work years in resin tapping. Arthrosis deformans of the elbow joints is regarded by us to be a "resin-tapping related health risk", which is found in one in four resin tappers after about 18 work years.
Subject(s)
Energy Metabolism , Occupational Diseases/etiology , Work , Adult , Cross-Sectional Studies , Cumulative Trauma Disorders/epidemiology , Cumulative Trauma Disorders/etiology , Elbow Joint , Heart Rate , Humans , Joint Diseases/epidemiology , Joint Diseases/etiology , Male , Middle Aged , Occupational Diseases/epidemiology , Occupations , Stress, Physiological , TreesABSTRACT
In terms of social-insurance legislation, the small-scale private work of cooperative agricultural and horticultural workers has the same status as their cooperative-farm work. Therefore, it must be included in occupational-hygiene analyses for the evaluation of the physical work load. Continuous heart-rate measurements were carried out in 64 people-workers operating can-to-can or pipeline milking facilities, agricultural-machinery mechanics, female horticultural workers and tractor or harvester drivers-covering a total of 138 working days. Only considering the cooperative-farm work-load, it is only the milking-facility workers whose work can be evaluated as hard. Including the additional private agricultural work too, the work of the female horticultural workers also must be evaluated as hard, and that of the agricultural-machinery mechanics as moderately hard. In the case of the tractor and harvester drivers, the private small-scale agricultural work in occupational-health terms is regarded as a favourable counter-balance to the hypokinesia involved in driving.
