Abstract  Index for communications between US EPA and state of Utah regarding asbestos-containing materials in schools: state request for waiver from requirements / Asbestos-Containing Materials in Schools: State Request for Waiver from Requirements Docket No. 62091

Abstract  In Canada, both federal and provincial governments have responsibilities related to drinking water. In general, provincial governments a~e responsible for an adequate, safe supply, whereas the federal Department of National Health and Welfare develops quality guidelines and conducts research. The Guidelines for Canadian Drinking Water Quality were published in 1978 and includes maximum acceptable concentrations for 21 organic chemicals of health concern, 16 of which are pesticides. These guidelines are now being revised through a joint federal-provincial mechanism, with particular emphasis being placed on organic contaminants. The World Health Organization published revised drinking water quality guidelines in 1984 including health related guidelines for 18 organic. chemicals, 8 of which are pesticides.

Abstract  Cell transformation models have been established for studying the cellular and molecular basis of the neoplastic process. Transformation models have also been utilized extensively for studying mechanisms of chemical carcinogenesis and, to a lesser degree, screening chemicals for their carcinogenic potential. Complexities associated with the conduct of cell transformation assays have been a significant factor in discouraging broad use of this approach despite their reported good predictivity for carcinogenicity. We previously reported that many of the experimental difficulties with the Syrian hamster embryo (SHE) cell transformation assay could be reduced or eliminated by culturing these cells at pH 6.7 culture conditions compared to the historically used pH 7.1-7.3. We and others have shown that morphological transformation (MT), the earliest recognizable phenotype in the multi-step transformation process and the endpoint used in the standard assay to indicate a chemica

Abstract  INTRODUCTION: Epigenetic inactivation of tumor suppressor genes is involved in the development of malignant pleural mesothelioma (MPM). ZIC1, a potential tumor suppressor gene involved in regulating cell growth and apoptosis, was investigated in MPM cell lines and tumors.

METHODS: ZIC1 expression and promoter methylation were evaluated in MPM cell lines and tumor samples by quantitative polymerase chain reaction (PCR), Combined Bisulfite Restriction Analysis, and methylation-specific PCR. ZIC1 was reexpressed in cell lines and functional effects were assessed. miRNA expression was quantified by microarray and reverse transcription quantitative PCR. ZIC1 knockdown and miRNA inhibitors were used to study the relationship between ZIC1 and miRNA expression and confirmed by chromatin immunoprecipitation PCR.

RESULTS: ZIC1 expression was low in MPM cells, and was correlated with ZIC1 promoter methylation and reversed upon decitabine treatment. ZIC1 reexpression inhibited proliferation and invasion in MPM cells whereas knockdown enhanced the growth of MeT-5A. In MPM tumor samples ZIC1 expression was either low or undetectable, with promoter methylation observed in 16 of 24 cases. The overexpression of miR-23a and miR-27a was reduced by ZIC1 reexpression, with inhibitors of miR-23a or miR-27a reducing colony formation. miR-23a overexpression was also associated with shorter survival of MPM patients.

CONCLUSION: ZIC1 is down-regulated in MPM through promoter methylation and acts as a tumor suppressor through down-regulation of its direct targets miR-23a and miR-27a.

Abstract  Oxidative stress is implicated as an important molecular mechanism underlying fibrosis in a variety of organs, including the lungs. However, the causal role of reactive oxygen species (ROS) released from environmental exposures and inflammatory/interstitial cells in mediating fibrosis as well as how best to target an imbalance in ROS production in patients with fibrosis is not firmly established. We focus on the role of ROS in pulmonary fibrosis and, where possible, highlight overlapping molecular pathways in other organs. The key origins of oxidative stress in pulmonary fibrosis (e.g. environmental toxins, mitochondria/NADPH oxidase of inflammatory and lung target cells, and depletion of antioxidant defenses) are reviewed. The role of alveolar epithelial cell (AEC) apoptosis by mitochondria- and p53-regulated death pathways is examined. We emphasize an emerging role for the endoplasmic reticulum (ER) in pulmonary fibrosis. After briefly summarizing how ROS trigger a DNA damage response, we concentrate on recent studies implicating a role for mitochondrial DNA (mtDNA) damage and repair mechanisms focusing on 8-oxoguanine DNA glycosylase (Ogg1) as well as crosstalk between ROS production, mtDNA damage, p53, Ogg1, and mitochondrial aconitase (ACO2). Finally, the association between ROS and TGF-β1-induced fibrosis is discussed. Novel insights into the molecular basis of ROS-induced pulmonary diseases and, in particular, lung epithelial cell death may promote the development of unique therapeutic targets for managing pulmonary fibrosis as well as fibrosis in other organs and tumors, and in aging; diseases for which effective management is lacking. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease.

Abstract  The generation of reactive oxygen species and other radicals, catalyzed by iron ions at the fiber surface, is thought to play an important role in asbestos-induced cytotoxicity and genotoxicity, but a direct confirmation of this statement needs the availability of asbestos samples differing only for their iron content, without the interference of other physicochemical features. Synthetic stoichiometric chrysotile nanofibers, devoid of iron or any other contaminant, did not exert genotoxic and cytotoxic effects nor elicited oxidative stress in a murine alveolar macrophage cell line; on the contrary, the same nanofibers, loaded with 0.57% and 0.94% (w/w) iron, induced DNA strand breaks, lipoperoxidation, inhibition of redox metabolism and alterations of cell integrity, similarly to natural chrysotile. On the other hand, the incubation with ferric nitrilotriacetate, a cell-permeating iron complex, even if it caused an intracellular overloading of iron very similar to that elicited by iron-loaded synthetic chrysotile and by natural chrysotile, did not exert any of these effects. This suggests that chrysotile is not toxic by acting simply as a carrier of iron into the cell, but rather that the redox activity of iron is potentiated when organized at the fibers surface into specific crystallographic sites having coordination states able to activate free radical generation. Synthetic chrysotile fibers may be proposed as a standard reference sample and model solids for experimental studies on asbestos fibers aiming to clarify the mechanisms of its toxicity and to synthesize new fibers devoid of pathogenic effects.

Abstract  The highly polymorphic N-acetyltransferases (NAT1 and NAT2) are involved in both activation and inactivation reactions of numerous carcinogens, such as tobacco derived aromatic amines. The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls. In addition to the wild-type allele NAT1*4, seven variant NAT1 alleles (NAT1*3, *10, *11, *14, *15, *17 and *22) were analysed. A new method based on the LightCycler (Roche Diagnostics Inc.) technology was applied for the detection of the polymorphic NAT1 sites at nt 1088 and nt 1095. The NAT2 polymorphic sites at nt 481, 590, 803 and 857 were detected by polymerase chain reaction-restriction fragment length polymorphism or LightCycler. Multivariate logistic regression analyses were performed taking into account levels of smoking, age, gender and occupational exposure. An increased risk for adenocarcinoma among the NAT1 putative fast acetylators [odds ratio (OR) 1.92 (1.16-3.16)] was found but could not be detected for SCC or the total case group. NAT2 genotypes alone appeared not to modify individual lung cancer risk, however, individuals with combined NAT1 fast and NAT2 slow genotype had significantly elevated adenocarcinoma risk [OR 2.22 (1.03-4.81)] compared to persons with other genotype combinations. These data clearly show the importance of separating different histological lung tumour subtypes in studies on genetic susceptibility factors and implicate the NAT1*10 allele as a risk factor for adenocarcinoma, Pharmacogenetics 11:157-168 (C) 2001 Lippincott Williams & Wilkins.

Abstract  Laboratory studies with animals exposed to high concentrations of fine fibrous dust (fibrils) derived from para-aramid fibres suggest that it may cause lung damage. A survey was undertaken in a selection of manufacturers of para-aramid-containing products to assess their 8-h time-weighted average exposure to respirable fibrils. Geometric mean concentrations for different jobs were generally low. Assuming a log-normal distribution, less than 1% of the exposure levels would be expected to exceed 0.5 fibres/mL and about 0.002% would be above 2 fibres/mL. Analysis of a selection of samples by fluorescence microscopy suggests that most of the fibrils in the majority of sites surveyed were para-aramid. At some sites a significant proportion of asbestos fibres were also found.

Abstract  Paediatric mesothelioma is a very rare entity. We report here epidemiologic data from 489 cases reported in international medical literature. A better knowledge about this entity is mandatory to improve its management. triangle

Abstract  Alveolar macrophages are thought to play a major role in the pathophysiology of lung diseases caused by exposure to various kinds of pathogens and particles. In the present study, the cytotoxic effect of potassium octatitanate whisker (PT) on macrophages was evaluated by means of magnetometry, lactate dehydrogenase (LDH) release measurement, apoptosis measurement and morphological observations. Alveolar macrophages obtained from Fischer rats (F344/N Slc) by bronchoalveolar lavage were incubated in vitro for 18 h with Fe3O4 as a magnetometric indicator, and PTs as test materials. In the control group and the group exposed to 10 mug/ml of PT, rapid attenuation of the remanent magnetic field (RMF), so called "relaxation," was observed immediately after cessation of the external magnetic field. In comparison, a delay of relaxation was observed in alveolar macrophages exposed to 20 and 40 mug/ml of PT. The decay constants, which are calculated from decreasing RMF for the first 2 min, in the groups exposed to 20 and 40,ug/ml of PT had significantly lower values than the control. LDH release induced by exposure to 20 and 40,mug/ml of PT increased significantly in a concentration dependent manner in PT-exposed macrophages, whereas only negligible LDH release was observed in control groups. The level of PT affecting alveolar macrophages was at the same concentration, and in a dose-dependent manner among relaxation, decay constant and LDH measurement. A DNA ladder detection method and morphological observations detected no apoptosis in PT-exposed macrophages. Electron microscopic examination revealed vacuolar changes and cell membrane damage in PT-exposed macrophages, but no significant changes in control macrophages. The results of magnetometry, LDH release, apoptosis measurement and electron microscopic observations suggest concentration dependent cytotoxicity caused by exposure of alveolar macrophages to PT.

Abstract  Respiratory disease associated with occupational dust exposure remains a problem despite advances in exposure control. This paper reviews the evidence that chronic nonspecific airflow obstruction leading to chronic obstructive pulmonary disease (COPD) is linked to workplace exposures, in some cases even when exposures are below current regulated standards, Exposures discussed include mineral and metal dust and fumes, including those from coal, silica, asbestos, welding, and metal smelting, and organic dusts such as wood, grain, and mixed agricultural exposures. Emphasis is placed on the role of these exposures in association with airflow obstruction in nonsmokers and on the interaction between exposure and smoking. Evidence is discussed that suggests excess airflow obstruction in young workers may be linked to a worse ultimate prognosis. We argue that, for prevention of further deterioration, clinicians should routinely discuss occupational exposures with their COPD patients, as they do smoking cessation.

Abstract  Study objectives: Intrapleural immunotherapy has shown some activity in patients with malignant mesothelioma. We conducted a multicentric pilot phase II study to evaluate the tolerance and the activity of intrapleurally infused autologous human activated macrophages (AMPhi) in patients with stage IA, IB, and IIA malignant pleural mesothelioma (MPM).

Design: AM(D derived from in vitro monocyte culture were infused into the pleura of patients every week for 8 consecutive weeks. Each infusion was followed 3 days later by an intrapleural injection of 9 millions units of gamma-interferon (gamma-IFN) in an attempt to prolong the in vivo activation of infused AMPhi. Response was assessed by CT scan and thoracoscopy when possible. If the patient's disease progressed after A-NI(D treatment, an additional treatment was left to the choice of the investigator.

Patients: Nineteen patients with histologically proven stage IA, IB, or IIA MPM were enrolled. Two patients were excluded before any AMPhiD infusion because of complications impeding infusion. Seventeen patients were actually treated. After completion of the AMPhi cellular therapy, 10 patients were treated with chemotherapy as their diseases progressed.

Results: The overall response rate of patients actually treated was 14%. When including the two patients enrolled but not treated, the overall response "in intention to treat" was 11%; two patients had a partial response, with a duration of response of 30 months and 3 months, respectively. One patient, who could not be evaluated by thoracoscopy because of pleural symphysis, is still alive without any clinical or radiologic sign of disease 69 months after treatment. No major adverse effects were observed during the infusion of either AMPhi or gamma-IFN, and there was no interruption of treatment because of toxicity. However, symphysis was observed in 7 of 14 patients who received the complete treatment. The median survival of patients actually treated, including those who received chemotherapy after AMPhi, was 29.2 months.

Conclusion: Combined infusion of A-MPhi and gamma-IFN was well tolerated in patients with MPM; however, it had limited antitumor activity.

Abstract  Background In a recent analysis of a UK cohort Sorahan and Harrington [2007: Am J Ind Med 50: 555-564] assessed the most recent 15 years of exposure ("lugging") to support their hypothesis that carbon black acts as a late stage lung carcinogen. We tested this metric in a German cohort of 1,528 carbon black workers.

Methods We used a multi-model Cox regression approach (720 models) to explore the impact of duration and cumulative exposure to carbon black "lugged" by 0, 5, 10, 15, and 20 years. This approach covered four sub-cohorts, including an inception cohort, different exposure scenarios and varying combinations of confounders.

Results Seven hundred nineteen models returned negative coefficients. Only one model estimated a small positive, but clearly non-significant coefficient (P = 0.8).

Conclusions Despite extensive searching, no exposure scenario suggested an adverse effect of "lugged" carbon black exposure on lung cancer mortality Our analysis does not support the hypothesis of carbon black being a late stage carcinogen. Am. J. Ind. Med. 52:890-899, 2009. (C) 2009 Wiley-Liss, Inc.

Abstract  BACKGROUND: Idiopathic retroperitoneal fibrosis (RPF) is a rare disease. Asbestos exposure has been proposed as a risk factor for idiopathic RPF.

OBJECTIVE: To investigate the role of asbestos and other occupational agents (such as silica, metals, and organic solvents), as well as environmental agents (such as smoking), and their interactions as potential risk factors for idiopathic RPF.

DESIGN: Case-control study.

SETTING: National referral hospital for idiopathic RPF.

PATIENTS: 90 patients with idiopathic RPF and 270 control participants matched for age, sex, and region of residency.

MEASUREMENTS: Occupational history was obtained using structured questionnaires administered by blinded specialists in occupational medicine. Exposure to nonoccupational agents and presence of diseases that were potentially predisposing to idiopathic RPF were assessed through patient interviews and examination of medical records.

RESULTS: A history of asbestos exposure was associated with idiopathic RPF (odds ratio [OR], 4.22 [95% CI, 2.14 to 8.33]). Both current smoking (OR, 3.21 [CI, 1.46 to 7.07]) and former smoking (OR, 2.93 [CI, 1.39 to 6.14]) were more prevalent among patients than among those who never smoked. A multiplicative effect was found between tobacco smoke and both occupational asbestos exposure (OR, 12.04 [CI, 4.32 to 38.28]) and extraoccupational asbestos exposure (OR, 8.42 [CI, 2.77 to 30.58]).

LIMITATION: Retrospective, questionnaire-based assessment of occupational exposure.

CONCLUSION: Exposure to asbestos and tobacco smoke resulted in strong risk factors for idiopathic RPF. Coexposure to asbestos and smoke had a multiplicative effect on risk compared with single exposure.

PRIMARY FUNDING SOURCE: None.

Abstract  This review describes the structure, physicochemical properties and sources of asbestos as well as other mineral fibres in the natural environment. The diversity of character and methods for the determination of airborne inorganic fibres are discussed with particular attention to the biological effects on humans health. It also demonstrates the practical significance of asbestos.

This article also shows some possibilities transformation of asbestos containing materials into harmless products.

Abstract  Owing to the high rates of malignant mesothelioma in workers exposed to crocidolite earlier at Wittenoom and evidence of protection against cancer by vitamin A, a population-based cancer prevention programme providing retinol supplements (25 000 IU/day) was commenced in 1990. The former workers at Wittenoom known to be alive and living in Western Australia in June 1990 constitute the study population. The participants were classified into two groups: those who received supplemental retinol (intervention group) and those who received none (comparison group). The relative rate of mesothelioma for those receiving retinol was estimated using Cox regression, adjusting for cumulative asbestos exposure and age at first exposure to asbestos. Nine hundred and twenty-eight former Wittenoom workers received retinol at some stage of the programme, whereas 1471 workers never received retinol (comparison group). Those who received retinol were younger, had a greater exposure to asbestos and smoked less than the comparison group. There were 65 cases of mesothelioma in the retinol group and 88 in the comparison group. After adjustment, the hazard ratio was 0.99 (95% confidence interval=0.70-1.41). This result did not alter when the participants who received only retinol once or those who received beta-carotene earlier were excluded from the analysis. In conclusion, this study provides little support for possible preventive effects of retinol against mesothelioma in workers exposed to blue asbestos.