We have observed that in three human malignant mesothelioma cell lines, crocidolite asbestos induced the activation of the transcription factor NF-kappaB and the synthesis of nitric oxide (NO) by inhibiting the RhoA signaling pathway. The incubation with crocidolite decreased the level of GTP-bound RhoA and the activity of Rho-dependent kinase, and induced the activation of Akt/PKB and IkBalpha...

Erionite and crocidolite fibers were tested for carcinogenicity by intrapleural and intraperitoneal injection (una tantum) in 40 Sprague-Dawley rats per route for each fiber type. Pleural mesotheliomas were found in nine of ten animals that died within a year after intrapleural injection with erionite fibers. No pleural tumors were found among the animals treated at the same time and in the sam...

Fiber length and diameter are important factors in the pathogenicity of asbestos. We examined the relative toxicity of long and short crocidolite asbestos fibers in vitro and in vivo. Both long and short crocidolite asbestos fibers were toxic to elicited macrophages in vitro. Similar to native crocidolite asbestos, long and short fibers stimulated the release of reactive oxygen metabolites from...

BACKGROUND Asbestos induces DNA and chromosomal damage, but the DNA repair pathways protecting human cells against its genotoxicity are largely unknown. Polymorphisms in XRCC1 have been associated with altered susceptibility to asbestos-related diseases. However, it is unclear whether oxidative DNA damage repaired by XRCC1 contributes to asbestos-induced chromosomal damage. OBJECTIVES We soug...

Nuclear factor kappa B (NF-kappa B) is a transcription factor that regulates expression of several genes coding for inflammatory and immunoregulatory proteins including the neutrophil chemotactic cytokine MIP-2. In previous studies we found that crocidolite asbestos activates the nuclear translocation of NF-kappa B as well as MIP-2 gene expression in rat alveolar type II cells. Here we report t...

Crocidolite is a well-known causative agent for mesothelioma. However, studies have shown that the pathogenicity of the fiber from different mines varies considerably and it has been postulated the parameter that appears most likely to account for this variation is fiber width although this has never been formally confirmed. To date, crocidolite appears to be the only asbestos mineral for which...

Asbestos fibers cause persistent induction of the oxidative stress sensitive transcription factors nuclear factor kappa-B (NF-kappa B) and activator protein-1 (AP-1) in mammalian cells. These transcription factors play an important role in the regulation of cellular activity. Lipid peroxidation, mediated by reactive oxygen species, is thought to be a possible mechanism in the pathogenicity of a...

Biological modification of asbestos fibers can alter their interaction with target cells. We have shown that vitronectin (VN), a major adhesive protein in serum, adsorbs to crocidolite asbestos and increases fiber phagocytosis by mesothelial cells via integrins. Because chrysotile asbestos differs significantly from crocidolite in charge and shape, we asked whether VN would also adsorb to chrys...

The results of analysis of mineral fibres in lung tissues from 10 paraoccupational cases of malignant mesothelioma were compared with analysis obtained from seven cases of malignant mesotheliomas that had developed in gas mask workers. Nine of the paraoccupational cases were considered to have developed their tumours because of exposure to asbestos on their husbands' working clothes and one can...

Fiber length and diameter are important factors in the pathogenicity of asbestos. We examined the relative toxicity of long and short crocidolite asbestos fibers in vitro and in vivo. Both long and short crocidolite asbestos fibers were toxic to elicited macrophages in vitro. Similar to native crocidolite asbestos, long and short Tibers stimulated the release of reactive oxygen metabolites from...