Inflammatory effects of respirable quartz collected in workplaces versus standard DQ12 quartz: particle surface correlates.

In 1997, the IARC (International Agency for Research on Cancer) reevaluated its quartz classification from a class 2 carcinogen, to that of a class 1, stating sufficient evidence for carcinogenicity in both humans and experimental animals. However, tumor development did not occur across all occupational settings. It is probable that this is due to the considerable differences in toxicity between workplace quartz in comparison to quartz used in experimental studies. We therefore hypothesized that workplace quartz samples differ in toxicity from standard experimental quartz samples at equal mass. To test this hypothesis we compared 2 workplace quartz samples (RH1 and OM) with standard experimental quartz (DQ12) in several assays commonly used in particle toxicology. The sizes of the quartz samples were as closely matched as possible. The endpoints of this study were inflammation in the rat lung following intratracheal instillation (1000 microg or 250 microg for 3 or 14 days), release of soluble iron, cytotoxicity to cells in culture, and surface reactivity as assessed by hemolysis and ESR. The workplace samples did not cause inflammation at any dose or time point. DQ12 quartz caused marked inflammatory responses, as measured by an increased number of neutrophils in the lungs of instilled animals for both time points and doses. Protein in the bronchoalveolar lavage also increased in animals exposed to DQ12 but not the workplace samples. In vitro, DQ12 had the greatest hemolytic activity but only RH1 released substantial amounts of soluble iron. The increased inflammogenicity of DQ12 was not wholly explained by a greater surface area, by diameter, or by releasable iron. The hemolytic activity of DQ12, while not being informative in terms of understanding the mechanism of carcinogenicity, was the best in vitro predictor for in vivo activity. Therefore the surface reactivity of DQ12 appears to drive its inflammogenicity.

Clara-cell hyperplasia after quartz and coal-dust instillation in rat lung.

Bronchiolo-alveolar hyperplasia of type II cells in rat lungs after particle exposure is a well-known preneoplastic lesion. The Clara cell, stem cell of the bronchiolar epithelium and the main carrier of cytochrome P-450 isoenzyme system in the lung, has barely been evaluated with regard to this effect. The aim of this study was to examine Clara-cell hyperplasia after particle exposure and to characterize cell proliferation and its normal function. Female Wistar rats were intratracheally instilled with coal dust samples of variable quartz content, quartz (DQ12), titanium dioxide, or saline solution containing 0.5% Tween 80. After 126-129 wk, all coal mine dust- and quartz-exposed animals developed Clara-cell hyperplasia: up to 0.48% of the total lung area, which was significantly increased compared to titanium dioxide (p <.05) and control (p <.03) animals. Proliferation and hyperplasia of bronchiolar Clara cells by coal dusts was independent of their quartz content. The lack of proliferating cell nuclear antigen staining in most of the hyperplastic Clara cells suggests that following damage of alveolar epithelial cells, Clara cells migrate in and remodulate the alveolar epithelium. After the migration they keep their function in the xenobiotic metabolism, as shown by expansion of CYP2E1 active Clara cells. The minor development of Clara-cell hyperplasia in titanium dioxide-treated rats indicates that this is not a general particle effect, and is possibly due to its lower toxicity to epithelial cells.

Chronic Inflammation and Tumor Formation in Rats After Intratracheal Instillation of High Doses of Coal Dusts, Titanium Dioxides, and Quartz.

Coal mine dust's possible carcinogenicity has recently drawn attention because of the IARC review of quartz, some new epidemiological data in German coal miners, and findings on other poorly soluble, nontoxic dusts in the rat. The aim of this study was to investigate persistent inflammation and tumor response in the rat after intratracheal instillation of two coal dust samples and other dust preparations. Female Wistar rats (190 g) were instilled with ground lean coal (60 mg) coal mine dust (60 mg), DQI2 quartz (5 mg), and fine (60 mg) and ultrafine (30 mg) TiO2. After 129 wk rats were killed, tumors detected by microscopy, and inflammation by light microscopy after specific antibody staining for macrophages and granulocytes. Increased alveolar macrophages (AM) and interstitial granulocytes were still present in dust-treated animals. Both AM and granulocytes per surface area were related to tumor incidence when all materials were plotted in one graph, and can be interpreted as effects of overload. Differences in tumor formation between fine and ultrafine TiO2, despite similar inflammatory response, are probably caused by a direct effect of ultrafine TiO2 after interstitialization. It is concluded that coal dust is another poorly soluble, nontoxic dust, which at high enough dose rate causes overload, inflammation, and tumor response in the rat.

[Physiologic and pathologic patterns of reaction to silicone breast implants]. / Physiologische und pathologische Reaktionsmuster auf Silikonprothesen der Mamma.

Local morphological reaction patterns on breast implants can be of high significance as possible starting point for controversely discussed systemic immune response triggered by silicon or silicone. Therefore, the collagenous capsules of 149 explanted mammoplasty prostheses were examined macroscopically, under a scanning electron microscope and light-microscopically using antibodies to the macrophage antigen CD68, vimentin, muscle actin, and the proliferation antigen MIB1, and were then correlated with anamnestic data (implanted type of prosthesis, indication for im- or explantation). According to our examinations, the in-vivo durability of the prostheses' shells is considerably decreasing with the expansion of their surfaces. Regardless of the type of the prostheses' surface regularly a chronic-proliferating inflammation pattern could be identified in the periprosthetic capsulectomy specimens starting with a synovial metaplasia of proliferating CD-68-negative and vimentin-positive mesenchymal cells in the area surrounding the implants and ending by its transformation into a stage of dense hyaline collagenous fibrous tissue after an advanced implantation period (> 2 years). By this, the texturing of the prosthesis surface modifies only the course, but not the quality of the chronically fibrosing inflammation. Bleeding of prosthesis as well as the incorporation of the polyurethane-foam coating of different prosthesis types into the periprosthetic breast capsule lead to a significant lymphoplasmacytic infiltration, partly with participation of local vessels as defined in a "silicone vasculitis". Morphological signs of an at least local immune response are detectable in 8.3% of the examined fibrotic capsules even without a morphologically identifiable foreign-body embedding. They can be possibly referred to- as well as the complete absence of hyaline collagenous fibrous tissue in 30% of the cases-a yet not causally clarified, inter-individually different susceptibility of the implant bearers. Only the systematic registration of the above-mentioned morphological reaction patterns in a "prosthesis-passport" together with the additional clinical observation of the patients can ensure in future the realistic estimation of potential health risks caused by silicone breast implants.

[Calcifying granulomatous peritendinitis after local dexamethasone treatment]. / Kalzifizierende granulomatöse Peritendinitis nach lokaler Dexamethasonbehandlung.

In this article we report on a 43-year-old man, who had been treated with two cortisone injections containing soja bean oil for epicondylitis humeri radialis. Four weeks after the second injection necrotized fat which had been extracted surgically was sent to us for histological examination. We could show a calcifying collagen fibre necrosis being cleared by a granulomatous reaction and resorbed by granulation tissue. The calcifying necrosis of collagen fibres might have been induced by soja bean oil which were used as carrier of the drug.

Renal aluminum excretion.

Urinary aluminum (Al) excretion was studied in humans with normal and impaired renal function. Al was measured by atomic absorption spectrometry. In healthy volunteers (n = 50), renal Al excretion was 12.2 +/- 8.5 micrograms/24 h. Two patients on plasma exchange therapy with normal renal function and an inadvertent load of 870 and 388 micrograms Al/treatment showed a 23 and 14% positive balance until next treatment. The renal pathway of excretion was shown to be important in 6 chronic renal failure patients on continuous peritoneal dialysis with residual renal function who eliminated in 24 h 51.4 +/- 24.0 micrograms Al by urine and only 27.2 +/- 18.4 micrograms Al across the peritoneum following a daily oral application of 342 mg Al. Studies with the isolated perfused rat kidney confirmed the limited renal capacity to eliminate Al. Al clearance declined from 0.75 to less than 0.08 mL/min when the kidney was perfused with 0.04-12.4 micrograms Al/mL medium. Al content of the kidney increased in a dose-dependent manner from less than 0.05 to 4.4 micrograms/kidney and reached saturation at 5 micrograms Al/mL medium.

Renal clearance of aluminium: studies in the isolated perfused rat kidney.

The model of isolated rat kidney was used to study the renal handling of aluminium (Al). The kidney function remained unchanged at perfusate concentrations of Al in a range of 0.04-12.4 micrograms/ml during a perfusion period of 60 min. The clearance values of Al decreased with increasing concentrations of Al in the perfusate. The fractional Al clearance was reduced from 70% at the lowest Al concentration in the perfusate to 8.2% at the highest Al concentration. The Al content of the kidneys increased dose-dependently and reached a maximum value of 4 micrograms Al per kidney at a perfusate concentration of 5 micrograms Al/ml. Protein-binding studies with Al confirmed the suggestion that renal elimination of Al is dependent on the degree of Al binding. It is proposed that at low Al load in the plasma, the kidney possesses the capability to eliminate Al in an effective manner.

Characterization of a new permanent squamous carcinoma line from human lung B 109.

A permanent squamous carcinoma cell line was established from human lung. The cells exhibit good growth characteristics in vitro and in nude mice. Many marker chromosomes were detected. Histological examination and electron micrographs of B109 revealed at least two morphologically different subpopulations. The presence of steroid receptors and tumor associated antigens defined by monoclonal antibodies is discussed with regard to previously published results.

Renal handling of cadmium and cadmium-metallothionein: studies on the isolated perfused rat kidney.

The isolated kidney perfusion model was used to study the uptake of Cd and metallothionein (MT)-complexed Cd. Cd2+ at concentrations above 40 nM strongly depressed the glomerular filtration rate (GFR), whereas MT-complexed Cd (Cd-MT) at concentrations of 0.8-920 nM had no effect on the GFR. In contrast to Cd2+, Cd-MT was readily reabsorbed by the kidney and uptake saturation for Cd-MT occurred at 240 nM. The maximal transport rate for Cd-MT calculated in this study was 18 pmoles Cd-MT . g-1 . min-1. The accumulation of Cd in the kidney was more efficient in the experiment using Cd-MT, in which case the Cd kidney contents were about 2-4 times higher than compared to CdCl2.

Characterisation of a cell line from a human lung lymphosarcoma. Abundance of vimentin-type intermediate filaments.

A cell line (HCL82) was established from a human lung lymphosarcoma. Cells exhibited a stable phenotype and remained nearly diploid with a modal chromosome number of 45-48, showing no significant aberrations. Cultures consisted of single elongated cells and irregular colonies. Ultrastructurally, mitochondria, golgi complexes, and large bundles of intermediate filaments were well developed; some cells contained virus-like particles. Filaments were composed of vimentin identified by immunofluorescence and gel electrophoresis. Reaction with monoclonal antibody OKT4 suggested a close relationship to T-helper cells. Cells did grow at clonal density but did not form tumors in nude mice.

[Changes in chrysotile in vivo]. / Untersuchungen zur Veränderung des Chrysotils in vivo.

In an animal experimentation rats received a single intratracheal injection of 2 mg chrysotile per animal. Quantitative energy dispersive x-ray microanalysis (EDXA) and selected area electron diffraction (SAED) patterns of the chrysotile fibres, obtained from lung tissue, were performed with the aid of a transmission-electronmicroscope (TEM). During a period of four months the chemical and physical instability of asbestos fibres were investigated. The results of microanalysis were compared with standard chrysotile A, UICC as a reference material. The magnesium-leakage of chrysotile fibres and in the diameter range below 0.1 micrometer was found to be time-depending and increased during the period of the experiment. Opposite to the contents of Ca, the Fe-concentration was not significantly higher. After two months already, a greater number of depleted chrysotile fibres could be analysed. If leakage of magnesium exceeded 80 percentage, the typical single crystal electron diffraction patterns of the chrysotile could not be obtained furthermore. EDXA and SAED are inevitable techniques of identify fibres, which been altered during the period of deposition in animal lungs. There was no evidence to suggest the formation of asbestos bodies during the period of experimentation.