Cell cycle checkpoint status in human malignant mesothelioma cell lines: response to gamma radiation

Knowledge of the function of the cell cycle checkpoints in tumour cells may be important to develop treatment strategies for human cancers. The protein p53 is an important factor that regulates cell cycle progression and apoptosis in response to drugs. In human malignant mesothelioma, p53 is generally not mutated, but may be inactivated by SV40 early region T antigen (SV40 Tag). However, the function of p53 has not been investigated in mesothelioma cells. Here, we investigated the function of the cell cycle checkpoints in six human mesothelioma cell lines (HMCLs) by studying the cell distribution in the different phases of the cell cycle by flow cytometry, and expression of cell cycle proteins, p53, p21WAF1/CIP1 and p27KIP1. In addition, we studied p53 gene mutations and expression of SV40 Tag. After exposure to γ-radiation, HMCLs were arrested either in one or both phases of the cell cycle, demonstrating a heterogeneity in cell cycle control. G1 arrest was p21WAF1/CIP1- and p53-dependent. Lack of arrest in G1 was not related to p53 mutation or binding to SV40 Tag, except in one HMCL presenting a missense mutation at codon 248. These results may help us to understand mesothelioma and develop new treatments

Role of Mutagenicity in Asbestos Fiber-Induced Carcinogenicity and Other Diseases

The cellular and molecular mechanisms of how asbestos fibers induce cancers and other diseases are not well understood. Both serpentine and amphibole asbestos fibers have been shown to induce oxidative stress, inflammatory responses, cellular toxicity and tissue injuries, genetic changes, and epigenetic alterations in target cells in vitro and tissues in vivo. Most of these mechanisms are believe to be shared by both fiber-induced cancers and noncancerous diseases. This article summarizes the findings from existing literature with a focus on genetic changes, specifically, mutagenicity of asbestos fibers. Thus far, experimental evidence suggesting the involvement of mutagenesis in asbestos carcinogenicity is more convincing than asbestos-induced fibrotic diseases. The potential contributions of mutagenicity to asbestos-induced diseases, with an emphasis on carcinogenicity, are reviewed from five aspects: (1) whether there is a mutagenic mode of action (MOA) in fiber-induced carcinogenesis; (2) mutagenicity/carcinogenicity at low dose; (3) biological activities that contribute to mutagenicity and impact of target tissue/cell type; (4) health endpoints with or without mutagenicity as a key event; and finally, (5) determinant factors of toxicity in mutagenicity. At the end of this review, a consensus statement of what is known, what is believed to be factual but requires confirmation, and existing data gaps, as well as future research needs and directions, is provided

Contrast Analysis in Latex/Surfactant Aqueous Suspensions

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In vitro response of rat pleural mesothelial cells to talc samples in genotoxicity assays (sister chromatid exchanges and DNA repair)

International audienceThe genotoxicity of three samples of talc has been determined using in vitro cell systems previously developed for testing asbestos fibres. The talc samples used consisted of particles of respirable size in order to test the effect of particles likely to be deposited in the lung. Genotoxicity was tested in cultures of rat pleural mesothelial cells (RPMC) using genotoxicity assays for unscheduled DNA synthesis (UDS) and sister chromatid exchanges (SCEs). The effects were compared with those obtained with negative controls (attapulgite and anatase) and positive controls (chrysotile and crocidolite asbestos). In contrast to asbestos, none of the talc samples, nor the negative controls, induced enhancement of UDS or SCEs in treated cultures in comparison with the untreated cultures

Fabrication of BN membranes containing high density of cylindrical pores using an elegant approach

International audienceA high quality BN membrane with millions of through cylindrical pores is simply fabricated using a double inversion approach combining atomic layer deposition and polymer-derived ceramic route. Well crystallized hexagonal boron nitride walls are obtained at relatively low temperature (1000 C). This new membrane is a promising candidate for osmotic energy conversion and water filtration applications