Study of the stability of a paramagnetic label linked to mesoporous silica surface in contact with rat mesothelial cells in culture.

Stable radicals detectable by electron paramagnetic resonance (EPR) may be use in the investigation of early events in cell-particle toxicity. Piperidine-N-oxyl derivatives (nitroxides), covalently linked to the surface of a high surface area silica (used as model solid for the technique), served as probes in the investigation of the effects of incubation of silica particles with mesothelial cells. A mesoporous silica (MCM-41), prepared by precipitation from a micellar solution, was the most appropriate silica-based particle for this purpose, as its channels allow direct contact with small molecules but not with macromolecules. The cytotoxicity of this amorphous silica is very low, allowing relatively high particle loading in the cell cultures. Both the high surface area of the sample and the large amount of inorganic material extracted from the cell culture provide enough material to run reasonably intense EPR spectra. Computer-aided analysis of the EPR spectra of silica-bound nitroxides provided information on the sensitivity of the labeled silica monitoring different environments, e.g., to follow the path of particles in a mammalian cell culture. Upon contact of the particles with mesothelial cells, the mean distance among the labels at the silica surface decreased as a consequence of the release of oxidizing and/or radical moieties from the cells

Pleuro-pulmonary tumours detected by clinical and chest X-ray analyses in rats transplanted with mesothelioma cells

New strategies for cancer therapy must be developed, especially in severe neoplasms such as malignant pleural mesothelioma. Animal models of cancer, as close as possible to the human situation, are needed to investigate novel therapeutical approaches. Orthotopic transplantation of cancer cells is then relevant and efforts should be made to follow up tumour evolution in animals. In the present study, we developed a method for the orthotopic growth of mesothelioma cells in the pleural cavity of Fischer 344 and nude rats, along with a procedure for clinical survey. Two mesothelioma cell lines, of rat and human origin, were inoculated by transthoracic puncture. Body weight determination and chest X-ray analyses permitted the follow-up of tumour evolution by identifying different stages. Autopsies showed that tumours localized on the whole pleural cavity (diaphragm, parietal pleura), mediastinum and pericardium. Tumour morphology and antigenic characteristics were consistent with those of the inoculated cells and were similar in both types of rats inoculated with the same cell type. These results demonstrate that mesothelioma formation in rats can be followed up by clinical and radiographic survey after gentle intrathoracic inoculation of mesothelioma cells, thus allowing the definition of stages of interest for further experimental trials. © 1999 Cancer Research Campaig

Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells

Cytotoxicity and mutagenicity of tremolite, erionite and the man-made ceramic (RCF-1) fibre were studied using the human– hamster hybrid A L cells. Results from these fibres were compared with those of UICC Rhodesian chrysotile fibres. The A L cell mutation assay, based on the S1 gene marker located on human chromosome 11, the only human chromosome contained in the hybrid cell, has been shown to be more sensitive than conventional assays in detecting deletion mutations. Tremolite, erionite and RCF-1 fibres were significantly less cytotoxic to A L cells than chrysotile. Mutagenesis studies at the HPRT locus revealed no significant mutant yield with any of these fibres. In contrast, both erionite and tremolite induced dose-dependent S1− mutations in fibre-exposed cells, with the former inducing a significantly higher mutant yield than the latter fibre type. On the other hand, RCF-1 fibres were largely non-mutagenic. At equitoxic doses (cell survival at ∼ 0.7), erionite was found to be the most potent mutagen among the three fibres tested and at a level comparable to that of chrysotile fibres. These results indicate that RCF-1 fibres are non-genotoxic under the conditions used in the studies and suggest that the high mesothelioma incidence previously observed in hamster may either be a result of selective sensitivity of hamster pleura to fibre-induced chronic irritation or as a result of prolonged fibre treatment. Furthermore, the relatively high mutagenic potential for erionite is consistent with its documented carcinogenicity. © 1999 Cancer Research Campaig

Negotiating stigmatisation of deviant behaviour: an exploration of locals’ perceptions of nude tourists

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