Malignant mesothelioma (MM) is an aggressive tumor associated with environmental or occupational exposure to asbestos fibers. Erionite is a fibrous zeolite, morphologically similar to asbestos and it is assumed to be even more carcinogenic. Onset and progression of MM has been suggested as the result of the cooperation between asbestos and other cofactors, such as SV40 virus infection. Nevertheless, several cases of MM were associated with environmental exposure to erionite in Turkey, where SV40 was never isolated in MM specimens. We show here that erionite is poorly cytotoxic, induces proliferating signals and high growth rate in human mesothelial cells (HMC). Long term exposure to erionite, but not to asbestos fibers, transforms HMC in vitro, regardless of the presence of SV40 sequences, leading to foci formation in cultured monolayers. Cells derived from foci display constitutive activation of Akt, NF-jB and Erk1/2, show prolonged survival and a deregulated cell cycle, involving cyclin D1 and E overexpression. Our results reveal that erionite is able per se to turn HMC into transformed highly proliferating cells and disclose the carcinogenic properties of erionite, prompting for a careful evaluation of environmental exposure to these fibers. The genetic predisposition to the effect of erionite is a separate subject for investigation. ' 2007 Wiley-Liss, Inc.

Asbestos fibre counting by phase-contrast microscope is subject to many sources of variation, including those dependent on the analyst. In this study, asbestos sample slides prepared with relocatable coverslips have been used for fibre counting among voluntary analysts to evaluate their proficiency. One slide of amosite and one of chrysotile were distributed to all the analysts, and three proficiency testing rounds were conducted for amosite and four for chrysotile. Each relocatable coverslip has a report in which are reported for each viewing field both the number of certified fibres (Verified Fibres) and a drawing representing the shape and position of the individual fibres. In the first round, the analysts were asked to report only the number of fibres counted in each of the predesignated fields of view. In the other rounds, subsequently developed, the analysts had to report the number and the position of the fibres for each field. The reported number of fibres and their position in each of the designed fields were evaluated against their respective verified fibres, to identify types of error. Discrepancies between reported fibres and verified fibres in each field of view have been used to evaluate the proficiency of the analysts. The discrepancies can be positive (D+) or negative (D−) depending on whether the analyst counts, for a specific field of view, more or less fibres compared to the verified fibres. The score is calculated using the following equation: Score = (1 − ∑D+ + ∑│D−│/VF) × 100. An analyst obtaining a score of ≥60, which corresponds to (∑D+ + ∑│D−│)/VF ≤ 0.40, is proficient. The number of laboratories that participating in this study varied from 13 to 17 depending on the rounds. For amosite fibre counts, the results were generally good compared to a proficiency score of 60. The major error made by analysts was the counting of fibres shorter than 5 µm, where this error was of 62% of extra fibres and accounted for 8% over-estimation of amosite fibres. For chrysotile, a score of ≥50 has been used to consider an analyst as proficient. The results of chrysotile fibres showed that in the first round all analysts counted less than fifty per cent of the verified fibres. In the second round 10 analysts out of 13 reached a score of ≥50, 8 of 16 in the third and 10 of 12 in the fourth. For chrysotile fibres, the error relating to the counting of fibres shorter than 5 µm was of 56% of extra fibres, but the error that most influenced the results was the number of oversight-missing fibres. This type of error accounted for 97% of the missing fibres and for the 29% under-estimation of the chrysotile fibres. For amosite fibre counting, results of this study show an improvement of the analyst’s performance. For the chrysotile fibre count, although there is a significant improvement in the comparison between some rounds, this is not continuous over time.