Thirteen samples of natural fibres and five samples of man-made fibres (MMF) were tested to determine their cytotoxicity and ability to produce chromosome missegregation in cultures in rat pleural mesothelial cells (RPMC). The natural samples included attapulgite, two amphiboles (amosite and crocidolite); seven consisted of chrysotile from various origins and three were obtained after chemical treatment of chrysotile. MMF included three refractory ceramic fibres (RCF) and two vitreous fibres (MMVF). All fibre samples were characterized by electron microscopic measurement of the fibre dimensions. Cytotoxicity was assayed on the basis of determination of mitochondrial integrity and chromosome missegregation by light microscopy examination of anaphases/telophases. The carcinogenic potency of 10 natural samples has been previously investigated using intrapleural inoculation in rats. It was therefore possible to establish correlations between in vitro and in vivo data obtained with the same set of samples. The various samples of chrysotile produced different in vitro effects, in agreement with the dispersion of response also observed in vivo. Cytotoxicity appears to be dependent on both fibre length and fibre diameter, as the longest or thickest fibres were the most toxic. The production of abnormal anaphases/telophases appears to depend on the presence of fibres of selected size, such as those previously defined by Stanton et al. (L > 8 micrograms; D < or = 0.25 microns); a threshold values was determined below which no abnormal anaphases/telophases were detected. This non-observable effect level was estimated to be 2.5 x 10(5) 'Stanton' fibres per cm2. There was no correlation between cytotoxicity and mesothelioma induction; in contrast, a correlation was found between the ability of a sample to produce chromosome missegregation in vitro and mesothelioma in vivo.

The cytogenetic effects of asbestos fibers on rat pleural mesothelial cells were studied in vitro. Crocidolite UICC significantly enhanced aneuploidy and produced few structural chromosome aberrations, whereas anatase, an isomorphic particle, induced no numerical or structural changes. Mitomycin C (300 nM) produced a tenfold increase in abnormal anaphases compared with controls. Asbestos produced anaphase/telophase abnormalities in a concentration-dependent manner. The majority of the abnormalities involved lagging chromosomes. Crocidolite UICC induced abnormalities at a dose of 7.0 micrograms/cm2, whereas Canadian chrysotile did so at 1.0 to 2.0 micrograms/cm2. When the response was assessed by the number of long and thin fibers per cm2 (length > 8 microns; diameter < or = 0.25 microns), crocidolite UICC produced more abnormalities than Canadian chrysotile at all concentrations. On a per-weight basis, these findings differ from those obtained after intrapleural inoculation, as crocidolite induced more mesotheliomas than chrysotile; however, on a per-fiber basis, the in vitro and in vivo effects were similar. These results show that anaphase/telophase analysis is sensitive and complementary to metaphase analysis, and suggest that asbestos might produce cell transformation by inducing chromosome missegregation and aneuploidy.

A retrospective study was conducted to evaluate lung retention of particles containing cerium in subjects with and without previous occupational exposure to mineral dusts. Analytical transmission electron microscopy was performed on 459 samples of bronchoalveolar lavage (BAL) fluid and 75 samples of lung tissue. Study of the distribution of mineralogical species in human samples showed that particles containing cerium were encountered in less than 10% of subjects. The proportion of subjects with particles containing cerium in their biological samples was not different between controls and subjects with previous occupational exposure to fibrous or nonfibrous mineral dusts. This was considered as the background level of lung retention of cerium in the general population. By contrast, determination of the absolute concentration of particles containing cerium in BAL fluid and lung tissue samples showed that 1 2% (from BAL fluid) and 15% (from lung tissue) of subjects with previous exposure to mineral particles had high lung retention of particles containing cerium. This study is believed to be the first one in which lung retention of cerium was estimated in the general population.

The abilities of Min U Sil quartz or tridymite particles to induce sister chromatid exchanges (SCEs) in cultures of human lymphocytes plus monocytes or of human purified lymphocytes were investigated. With cultures of lymphocytes plus monocytes the level of SCEs was significantly enhanced after treatment with tridymite at the highest dose tested (50 micrograms/cm2). No effect was observed with purified lymphocytes. Quartz did not give clear cut results. Complementary experiments with tridymite filtrates suggested that phagocytosis of tridymite particles by monocytes was a necessary step for the induction of SCEs in human lymphocytes.

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