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Asbestos fibres have been shown to stimulate the mitogen-activated protein kinase signalling cascade in rat pleural mesothelial (RPM) cells after autophosphorylation of the epidermal growth factor receptor (EGFR). We examined if mineral fibres with known carcinogenicity can be discriminated from materials with less or no carcinogenicity by their ability to up-regulate expression of EGFR protein in RPM cells in vitro. Crocidolite and erionite, two fibrous preparations with marked potential to induce mesothelioma, were associated with increases in EGFR protein expression over sham controls, whereas chrysotile asbestos and milled (non-fibrous) crocidolite did not. Intense patterns of EGFR protein expression were linked to RPM cells phagocytosing long fibres. To determine the role of EGFR expression in these cells, we assessed cell proliferation using an antibody against proliferating cell nuclear antigen (PCNA) in combination with an antibody against EGFR. In these co-localization studies, cells showed intense staining for EGFR protein 24 h before being PCNA positive at 48 h. These results suggest that carcinogenic fibres induce EGFR and initiate cell signalling cascades in mesothelial cells, leading to cell proliferation and carcinogenesis.

SUMMARY1. The role of uptake across the brush border in the intestinal absorption of calcium has been studied by examining the kinetics of influx into slices of rat intestine in vitro. Both mucosal and serosal surfaces were exposed to the medium.2. The rate of influx was accurately defined by a two-component expression comprising a saturable (Michaelis-Menten) term and a second term linear with concentration. Influx across the mucosal surface of closed sacs was similar, and the saturable component for slice influx could be ascribed mainly to transport across the mucosal surface. The half-saturation constant for Ca was near 1 mm. This component was predominant at normal luminal concentrations of free Ca in the duodenum of young rats, but less so in jejunum and ileum and in older rats.3. The same kinetic expression applied to Sr influx, with a half-saturation constant of 2-3 mm, and possibly also to Ba with an even higher value.4. The saturable component of Ca influx was greatly reduced by 2,4: dinitrophenol (DNP); influx was also inhibited by iodoacetate, cyanide and at 00 C. Inhibition commenced soon after exposure of the slices. A high concentration of DNP also caused an increase in the linear component of Ca influx. 5. The kinetics of Ca influx across the mucosal surface agreed closely with the kinetics of steady-state absorption of Ca either across the whole mucosal epithelium in vivo or across the entire intestinal wall in vitro. This agreement supports the hypothesis that Ca entry across the brush border is the rate-limiting step in absorption; such a hypothesis would allow net Ca translocation while preserving a low intracellular concentration of ionic Ca in the mucosal epithelial cells.

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