Monitoring and analysis of asbestos concentration in working environment of different asbestos-producing technologies in a certain area / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To analyze asbestos exposure level between 1984 and 2010 in a district of malignant mesothelioma with clustering incidence in Zhejiang Province, in order to improve the recognizing and early diagnosis of malignant mesothelioma, protect the health of workers.</p><p><b>METHODS</b>Monitoring data of total asbestos dust concentration in the air of workplace from 1984 to 2010 in asbestos textile enterprises, family hand spinning operation, brake production, and asbestos board production in Zhejiang Province were collected in the local CDC. A total of 766 TWA copies of mass concentration were collected, and 1233 copies of MAC data. Asbestos mass concentration and fibre counting concentration of 29 points of family hand spinning operation were parallel determinated in the same time and the same sampling point. Raw asesbtos materials and dust composition of local asbestos processing corporations were collected and analyzed using X-ray diffraction method.</p><p><b>RESULTS</b>Raw materials of asbestos used between 1984 and 2010 in this area were chrysotile from Sichuan, Qinghai, Xinjiang, Russia, Zimbabwe, and some were mixed with SiO2, CaCO3 and other impurities. Raw materials used in asbestos board production were blue asbestos. Dust concentration between 1960s and 1980s in asbestos processing plants far exceeded the national standard. After then the dust concentration decreased significantly, but still higher than the national standard. 95.2% of air dust concentrations in the workplaces of asbestos factories exceeded the standard, and dust concentrations of workplaces of raw material, spinning, weaving, carding and labor insurance were above 90% in which carding work had the highest median concentration. 37.9% of dust mass concentrations in hand spinning work exceeded the standard where textile machinery side had the highest value. Beating job in asbestos board manufacturing and grinding job in brake production had higher concentrations.</p><p><b>CONCLUSIONS</b>Most of production technologies in asbestos processing industry exceed the standard level, indicating that the workers were at risk for malignant mesothelioma and other asbestos related diseases, which should draw high attention.</p>

Foreign Body Reaction and Expression of Matrix Metalloproteinases/Tissue Inhibitor of Metalloproteinase by Injection of Mineral Fibers in Rats

BACKGROUND: The host response to natural fibers results in granuloma formation in an effort to limit tissue destruction. Matrix metalloproteinases (MMPs) are important molecules in the inflammatory granulomatous or reparative reaction. Here, we studied the foreign body reaction that occurs following natural fibers implantation by investigating MMPs and tissue Inhibitor of MMPs (TIMPs) in an in vivo model. METHODS: Female Sprague-Dawley rats were treated with crocidolite fiber or fibrous talc via subcutaneous and intraperitoneal injections and immunohistochemistry was conducted to confirm the expression of MMPs and TIMP-2 in tissue sections. RESULTS: We identified that mineral fibers elicited granulomas. Fibrous talc or intraperitoneal injection resulted in larger granulomas and severe tissue destruction compared with the lesions induced by crocidolite or subcutaneous injection. The expression of MMPs was elevated while granulomatous lesions were formed. The relative levels of MMPs were lower in the talc injected or intraperitoneal route models than those of crocidolite injected or subcutaneous injection models during the entire experiment. CONCLUSIONS: These findings demonstrate that specific expression of MMPs/TIMP is inversely related to the grade of tissue destruction and suggest that expression of MMPs is required for promoting granuloma formation and limiting tissue destruction.

Respiratory Symptoms, Pulmonary Function Tests, and Asbestos Related Chest Radiograph Abnormalities of Former Asbestos Textile Factory Workers / 대한산업의학회지

OBJECTIVES: The objective of this study was to examine the prevalence of respiratory symptoms, asbestos-related chest radiograph abnormalities and abnormal pulmonary function tests among former asbestos textile factory workers and to reveal the related factors of these abnormal findings. METHODS: There were 119 persons former asbestos textile industry workers registered in the health management pocketbook. Of 97 retired asbestos workers living in Busan, Yangsan and Gimhae, 63(64.9%) retired asbestos workers were enrolled into this study. The researchers administered questionnaires, and performed chest radiographys, and pulmonary function tests (PFT) on participants. The survey was conducted during July, 2009. RESULTS: Among former workers the number of lung fibrosis, pleural plaque, pleural calcification, and pleural thickening was 13(20.6%), 6(9.5%), 3(4.8%), and 1(1.6%) in chest radiography, respectively. Asbestos-related disorders and abnormal pulmonary function test groups had higher prevalence of respiratory symptoms. Participants with crocidolite exposure or long latency period had higher asbestos-related x-ray findings or abnormal PFT findings. CONCLUSIONS: Former asbestos textile workers had a high rate of asbestos-related disorders. Workers with crocidolite exposure or having had a longer latency period had more asbestos-related disorders. Because gradual increase of asbestos related disorders among high asbestos exposure group is expected, sustained, and intensive management is needed for these former workers.

Compensation and Diagnosis of Asbestos Related Disease / 가정의학회지

Asbestos is a fibrous silicate that was widely used because of its heat resistance properties. Asbestos exposure affects workers involved in mining or processing asbestos or those involved in the use of asbestos in the shipbuilding, construction, and textile- and insulation-manufacturing industries. There are three commonly available types of asbestos; chrysotile (white asbestos), amosite (brown asbestos), and crocidolite (blue asbestos). All three have been associated with cancerous and non-cancerous lung disease. Asbestos-related diseases includes benign pleural effusion, pleural plaques, diffuse pleural thickening (a non-malignant disease affecting the lung lining), rounded atelectasis, asbestosis (a scarring of the lung tissue caused by asbestos), mesothelioma and lung cancer. Mesothelioma is a malignant pleural or peritoneal tumor that rarely occurs in patients who have not been exposed to asbestos. The latency period of most asbestos-related disease is 10 years or longer, asbestos-related disease remains an important public health issue. The clinical diagnosis of asbestos related diseases should be based on a detailed interview of the patient and occupational data on asbestos exposure, signs and symptoms, radiological and lung physiological findings and selected cytological, histological and other laboratory studies. Radiological imaging plays a pivotal role in the diagnosis and management of asbestos-related disease.

Burden of major cancers on years of life lost with premature death in crocidolite-contaminated area in Dayao / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To evaluate the effects of environmental low-dose exposure to crocidolite on people's health and the society. METHODS The mortality data of cancer between 1994 and 2003 in an environmental crocidolite-contaminated area was obtained from hospital medical records of Dayao Center for Disease Prevention and Control, and Dayao Public Health Bureau. The years of life lost with premature death (YLLs), was used to measure and assess the death, health losses and social burden of cancer in this area.</p><p><b>RESULTS</b>In the environmental crocidolite-contaminated area, lung cancer was the prime cause of death in all kinds of cancers between 1994 and 2003, followed by liver cancer, mesothelioma stomach cancer and colorectal cancer, with mortality 10.15/10(5), 9.04/10(5), 8.48/10(5), 3.96/10(5) and 3.55/10(5) respectively. The mortality of main cancer in male and female increased with age growing except that of breast cancer in female. Results showed that the types of leading cancers of YLLs were liver cancer, lung cancer, mesothelioma, leukemia and stomach cancer with YLLs 1981.39 person-year, 1886.63 person-year, 1799.23 person-year, 948.01 person-year and 754.18 person-year respectively. The distribution of YLLs was similar in both sexes, higher in the middle age group (aged from 15 to 44 years and 45 to 59 years) and lower in other age groups. The indirect economic loss resulting from lung cancer (15.02% of the total loss), liver cancer (13.98% of the total loss) and mesothelioma (13.01% of the total loss) was relatively great. The YLLs and the indirect economic loss attributable to environmental low-dose exposure to crocidolite were 3092.23 person-year and 5,175,800 Yuan respectively.</p><p><b>CONCLUSION</b>Lung cancer, liver cancer, mesothelioma, leukemia and breast cancer are the major cancers with an important impact on people's health and premature mortality in the environmental crocidolite-contaminated area. The impact of cancer mortality is more severer in those aged over 45 years. Social burden of cancer is the greatest in persons aged from 15 to 59 years. Policies and plans should be worked out for the protection of environment and the prevention of cancer.</p>

Resposta comparativa pleural in vivo e do mesotélio in vitro à exposição por diferentes fibras de asbesto / Comparison of in vivo pleural response and in vitro mesothelial response to different asbestos fibers

Os produtos derivados de asbesto são amplamente utilizados pelo setor industrial, sendo descritas diversas doenças relacionadas à sua exposição, entre elas, o tumor primário da pleura, ou mesotelioma. O mecanismo fisiopatológico da lesão pelas fibras de asbesto no espaço pleural ainda não está totalmente estabelecido. Entre os fatores possivelmente implicados estão os efeitos provocados por uma resposta inflamatória com migração celular e liberação de mediadores moleculares levando à necrose, apoptose e alterações na proliferação e fibrogênese. No entanto, existem dificuldades no estudo da resposta in vivo ao asbesto, principalmente em virtude da população multicelular da cavidade pleural. Neste sentido, tem sido preconizado na literatura o estudo envolvendo animais geneticamente modificados ou selecionados, a fim de melhor compreender o papel das diversas populações envolvidas neste processo. Neste trabalho, tivemos como objetivo estudar comparativamente a resposta inflamatória aguda no líquido pleural e em células mesoteliais em cultura expostas a diferentes fibras de asbesto. Para tanto, animais controle e geneticamente selecionados para alta (AIR max) e baixa (AIR min) resposta inflamatória, e células mesoteliais em cultura foram expostas às fibras de asbesto crocidolita ou crisotila. Após 4, 24 ou 48 horas foram avaliadas a produção das citocinas IL-1b, IL-6 e MIP-2. Adicionalmente, no modelo in vivo foi avaliado o perfil celular do líquido pleural e a expressão do Ra PDGF em RESUMO fragmentos de pleura, e no modelo in vitro a resposta celular de apoptose e necrose. Como resultados, as fibras de asbesto crocidolita e crisotila produziram, em animais AIR max, uma elevação significativa no líquido pleural de leucócitos, neutrófilos e da IL-1b em comparação aos controles e aos animais AIR min. Entretanto, não houve diferença no número de macrófagos, IL-6 e MIP-2. As células mesoteliais em cultura expostas tanto às fibras crocidolita quanto crisotila...

Asbestos-derived products are used thoroughly by industry. Several diseases related to asbestos exposition have been described, among them the primary tumor of the pleura mesothelioma. The mechanisms by which asbestos fibers produce injury to the pleural space are not clear. Among the factors possibly implicated are the effects secondary to an inflammatory response characterized by cellular migration and the release of molecular mediators leading to necrosis, apoptosis, cellular proliferation and fibrogenesis. However, it is difficulty to characterize the cellular response in vivo, mainly by virtue of the multi-cellular population present into the pleural cavity. Therefore, studies involving animals genetically modified or genetically selected have been proposed in the literature, in order to better understand the role of the several cellular populations involved in this complex process. In this study, our objective was to determine the inflammatory response of the pleural fluid and compare to the response of cultured mesothelial cells exposed to different asbestos fibers. Controls and mice genetically selected for high (AIR max) or low (AIR min) inflammatory response as well as mice cultured mesothelial cells were treated to crocidolite or chrysotile asbestos fibers. After 4, 24 or 48 hours the production of the cytokines IL-1b, IL-6 and MIP-2 were analyzed. In addition, the in vivo cellular profile of the pleural fluid and the Ra PDGF expression in the pleura fragments was documented. In parallel, the in vitro mesothelial cellular response of apoptosis and necrosis was quantified. Both asbestos fibers produced in AIR max mice a significant elevation in the pleural fluid total leukocytes, neutrophils and IL-1b levels in comparison to the controls and AIR min animals. However, no difference was found in the macrophage number, IL-6 and MIP-2 levels. Cultured mesothelial cells had a high apoptosis, necrosis...

Expression of phosphorylated ERK1/2 induced by crocidolite fibers in BEAS-2B cells / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the characteristic of the signal transduction in BEAS cells induced by the crocidolite fibers.</p><p><b>METHODS</b>The human respiratory airway epithelial cells BEAS-2B were cultured in vitro. The final 100 microg/ml crocidolite concentration and lOnM of epidermal growth factor were cocultured with BEAS-2B cells for 30 minutes and 120 minutes. Phosphorylated ERKl/2 and MEKl/2 were detected by Western Blotting using specific antibodies.</p><p><b>RESULTS</b>A rapid phosphorylation expression of ERK1/2 (molecular weight at 44 kD and 42 kD, also called as p44 and p42) was observed by treatment of the BEAS-2B cells with 100 microg/ml crocidolite or 100 ng/ml EGF (the proven activator of the ERK signaling pathway) at 30 minutes. This phosphorylation could be still detected by incubation the cells at 2 hours. However no expression was changed for the total ERKl/2 expression at 30 minutes or 120 minutes. Treatment of BEAS cells with 100 microg/ml crocidolite fiber or 100 ng/ml EGF led to the rapid increased phosphorylation of MEK1/2 at 30 minutes; similarly, the overexpression of MEK1/2 could last 2 hours.</p><p><b>CONCLUSION</b>The crocidolite induces the MAPK (ERK1/2 and MEK1/2) phosphorylation within a shorter time. It indicates that the MAPKs signals are involved in the process of crocidolite induced damage.</p>

A Case of Malignant Pleural Mesothelioma Induced by Crocidolite / 대한산업의학회지

Asbestos exposure may cause asbestosis, pleural plaques and benign pleural disease, and may give a predisposition to malignant mesothelioma in occupationally exposed workers. This case report describes a 50-year-old man, dying from histologically confirmed, diffuse, malignant mesothelioma after asbestos exposure. As a young man, he had been exposed at the workplace to crocidolite for 2 years, but he had no other known history of occupational or environmental asbestos exposure. The patient presented with chest pain and general weakness. Computed tomography showed bilateral irregular pleural thickening along both lower lateral chest walls and a low attenuating mass in the anterior portion of the left lobe. Pathological examinations revealed that it was an epithelial type with tubulopapillary structures and it tested immunohistochemically positive for antibodies against cytokeratin, calretinin and vimentin. The patient was started on chemotherapy but he died to the disease at ten months after the first onset of the symptoms. Mesothelioma is a rare neoplasm in the general population. Nevertheless, the importance of close medical surveillance of the high-risk population is emphasized, because of increased asbestos exposure.

CD59 mutation and DNA oxidative damage in A(L) cells induced by crocidolite fibers / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To determine the effects of buthionine sulfoximine (BSO) and free radical scavenger, dimethyl sulfoxide (DMSO), on mutation frequency and the formation of 8-hydroxydeoxyganosine (8-OHdG) induced by crocidolite fibers in human-hamster hybrid (A(L)) cells.</p><p><b>METHODS</b>The cytotoxicity and mutagenicity were determined by the formation of colonies. 8-OHdG was examined by immunoperoxidase staining. Non-protein sulfhydryl (NPSH) compound was assayed by modified Tietze's method.</p><p><b>RESULTS</b>The level of NPSH in A(L) cell pretreated with 25 micro mol/L of BSO was decreased to 2 nmol/10(7) cells, only 5% of the control after 24 h. The mutation frequency of CD59 gene of A(L) cell in crocidolite alone treated group was 208 +/- 18 while that in BSO pretreated group (397 +/- 55) was about twice the former (P < 0.05). The mutation frequency of CD59 gene in the group treated with crocidolite and in the presence of DMSO (57 +/- 8) was 72.6% less than that in crocidolite alone treated group. Crocidolite fibers induced a dose-effect relationship in the formation of 8-OHdG in A(L) cells (y = 150 + 20x, r = 0.9621). The level of 8-OHdG in cells was 289 +/- 6 at the dose of 6 micro g/cm(2) crocidolite, which was about twice the control group (137 +/- 9). In the presence of DMSO, 8-OHdG level decreased to 170 +/- 3 at the same dose of crocidolite.</p><p><b>CONCLUSION</b>Free radicals are the important inducer of mutagenesis and DNA damage in A(L) cells caused by crocidolite, which has dose-effect relationship.</p>

Risk factors for malignant pleural mesothelioma in crocidolite contaminated area / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To explore the risk factors for mesothelioma so as to provide epidemiological evidences for prevention of this disease and for further study of its pathogenesis.</p><p><b>METHODS</b>A 1:1 paired case-control study was carried out in which asbestos exposure, life style and histories of cancer in first-degree relatives of 23 patients who had mesothelioma were compared with those of controls.</p><p><b>RESULTS</b>The mean age of patients was 57.96 years with a latency period of 52 years. There were no significant differences in mean exposure age, mean exposure periods, and smoking, drinking habits between patients and controls. The mean cumulative exposure of patients was 37.2 x 10(5) f, which was significantly higher than that of controls (32.3 x 10(5) f, P = 0.005). The odds ratio increased with the cumulative exposure. The percentage of cancer in first-degree relative of patients (26.1%) was significantly higher than that of controls [(4.4%, P < 0.05), OR = 7.75 (95% CI: 0.85-71.43)].</p><p><b>CONCLUSION</b>There may be a dose-response relationship between mesothelioma and asbestos exposure. A family history of cancer may be a risk factor for mesothelioma, or may indicate an increased susceptibility to mesothelioma under the same level of asbestos exposure.</p>

Mesoteliomas malignos de la pleura: diagnóstico, tratamiento y evolución en una serie de 43 pacientes / Malignant pleural mesothelioma: diagnosis, treatment and follow-up in our experience with 43 cases

Antecedentes: Los mesoteliomas malignos de la pleura presentan una extrema gravedad. Actualmente han aumentado las observaciones, demostrando una corta y una mala supervivencia. Objetivo: Estudiar los procedimientos para su diagnóstico, estadificación y tratamiento. Analizar el pronóstico y la supervivencia. Lugar de Aplicación: Hospital Público, Sanatorio Privado. Diseño: Estudio Retrospectivo. Población: De 43 enfermos (lapso 1960-1997) 27 por ciento eran mujeres y 73 por ciento varones, con edades extremas de 10a 89 años. Padeció dolor torácico el 69,9 por cientoLocalización: 62,7 por ciento derecha y 37,3 izquierda. Se intervinieron quirúrgicamente 32 (74,4 por ciento) decorticaciones 24 (75 por ciento), neumonectomías 5 (15,6 por ciento), bilobectomía 1(2,3 por ciento) tóraco-lobectomía 1 (3,1 por ciento) y pleuroneumonectomía 1( 3 por ciento). Métodos: Se analizaron los antecedentes clínicos y epidemiológicos, el diagnóstico, las indicaciones quirúrgicas, el tipo de tratamiento y la superviviencia. Resultados: Sobrevivieron 13 enfermos a los 6 meses (40,6 por ceinto), 14 al año (43,7 por ciento). 1 a los 3 años (3,1 por ciento) y 1 a los 8 años (3,1 por ciento). Mortalidad operatoria intermedia: 1 (3,12 por ciento). Conclusiones: La profilaxis de la asbestosis, el diagnóstico temprano, una correcta estadificación y elección del tratamiento, incluyendo el estudio cooperativo de importantes grupos de trabajo, posiblemente alarguen y mejoren la supervivencia de estos pacientes

Effect of Desferrioxamine on Silica-Induced Cytotoxicity of A549 and Fibroblast Proliferation / 대한산업의학회지

The inhalation of crystalline silica results in the production of reactive oxygen species(ROS). Among these ROS, hydroxyl radical( OH) is believed to be the most reactive one. OH is generated in reaction between superoxide and hydrogen peroxide catalyzed by transition metal, especially iron. Therefore iron should be important in the bioactivity of crystalline silica. Desferrioxamine, a iron chelator, may be protective in silica-induced pulmonary reaction. To test this assumption we investigated the protective effect of desferrioxamine on lipid peroxidation of cell membrane, cytotoxicity, production of proinflammatory and chemotactic cytokine and fibroblast proliferation by crystalline silica in vitro model. The results were as follows: 1. Fenton activity of silica and asbestos was significantly higher than that of control. Fenton activity in crocidolite was higher than silica at the same dose. This result correlated with iron content of dust. Fenton activity of silica and crocidolite was decreased by preincubation of silica with desferrioxamine. 2. Silica induced a dose-dependent increase of MIDA concentration in lung epithelial cell lysate dose dependently. Marked decrease of MDA was observed in desferrioxaminetreated silica group compared with untreated group. 3. As concentration of stimulated silica, silica?induced cytotoxicity was increased. There was significant decrease of cytotoxicity in desferrioxamine?treated silica group compared with untreated group. 4. a-quartz augmented the production of TNF-a and IL-8 from A549 cell. While desferrioxa-mine suppressed the release of cytokines. 5. Supernatant of silica-cocultured A549 cell induced a significant proliferation of fibroblast, which desferrioxaime blocked this proliferation. From these result, we concluded that desferrioxamine has a protective effect on silica induced pulmonary reaction.

Analysis of Pulmonary Asbestos Body in Malignant Mesothelioma: A case report

The association between occupational asbestos exposure and the subsequent development of malignant mesothelioma of pleura is well recognized. We analyzed an asbestos body by energy dispersive X-ray analyser in a case of malignant mesothelioma of pleura who had a history of asbestos exposure 30 years ago. In transmission electron microscope, the asbestos body was composed of a core of refractile thin asbestos fiber bundle and beaded masses of electron-dense iron and protein complex. The core fibers were analyzed as an amphibole type crocidolite fiber [(Na2Fe3Fe2(Si8O22)(OH)2] which composed of high content of silicon, iron and sodium.

Relationship Between Mineral Fiber-Induced Pulmonary Tissue Reaction and MIP-2 / 대한산업의학회지

The pulmonary recruitment and activation of inflammatory cells, in particular, neutrophils is thought to contribute to lung injury resulting from dust exposure. MIP-2 (macrophage inflammatory protein-2) which is a member of C-X-C chemokine plays a key role in neutrophil recruitment to sites of tissue injury. Especially, mineral fiber induced pulmonary response is as a model for the neutrophil recruitment. Therefore, we evaluated the distribution of MIP-2 expression in lung tissue of mineral fiber exposed rat using immunohistochemical study and the relationship between degree of inflammation of lower respiratory tract and MIP-2 expression. Total cell counts in bronchoalveolar lavage (BAL) fluid in mineral fiber-exposed group were markedly increased compared with each control group even not in ceramic fiber group. Number of neutrophil in BAL fluid in mineral fiber-exposed group were markedly increased compared with each control group until 4th week but except ceramic fiber group. In chrysotile group, number of neutrophil in BAL fluid were markedly increased compared with control group at 8th week. Lung tissue instilled with all kinds of mineral fibers showed remarkable developments of bronchus associated lymphoid tissue (BALT) and small multiple granulomas but not for ceramic fiber group. In chrysotile group, multiple granuloma and inflammatory change were more profuse response compared with other groups. MIP-2 was predominently expresses in epithelial cells of bronchioles and bronchus and was express also found in macrophages with lung section at 1 week after fiber instillation. Small amount of epithelial cell associated MIP-2 was present in chrysotile at 8 week group. But MIP-2 was not seen in epithelial cells and macrophages in the lung tissue instilled with crocidolite, ceramic fiber and glass fiber at 8 weeks. Our finding suggest that MIP-2 is predominantly expressed in bronchial epithelial cells of lung from mineral fiber-exposed rat and correlated with inflammatory cell, especially neutrophil, recruitment and tissue reaction. And we documented that MIP-2 expression and neutrophil recruitment in man-made vitreous fiber-exposed rat, especially glass fiber, less than chrysotile.

Cytotoxicity and Apoptosis by Silica, Asbestos and Man-Made Mineral Fibers / 대한산업의학회지

Exposure to various particles and fibers can result in lung inflammation that may progress to fibrosis, even lung cancer for which there is no effective clinical treatment now. The mechanism involved in pulmonary injury has not been well defined ; however, most current evidence implicates a central role for alveolar macrophages (AM) in this process. Also apoptosis or programmed cell death is regarded as a mechanism which is related with the pulmonary fibrosis. We propose that the cytotoxic potential of various particles may be evaluated by measuring lactic dehydrogenase (LDH) from particle co-cultured supernatant and theses particles may induce the characteristics of apoptosis, DNA ladder. We analyzed rat AM culture media which was incubated for 3 days with the same concentration (10 ug/ml) of silica(Si), chrysotile(Ch), crocidolite(Cr), ceramic fiber(CF), rock wool(RW) and glass wool (GW). And each particles (50ug/cm(2)) was incubated with A549 (pneumocyte in tracheal epithelium) cell lines for 24 hours to confirm the DNA ladder. Additionally, silica induced apoptosis in vivo was confirmed by electromicroscopic observation. The results were as follows; 1. Silica, asbestos and man-made mineral fibers (MMMF) co-cultured with AM showed the increase of LDH significantly with the time interval of 24, 48, 72 hours except for ceramic fiber in 48 and 72 hours and crocidolite in 72 hours. 2. Silica, asbestos and man-made mineral fibers (CF, GF) showed the characteristics of apoptosis, DNA ladder, which was induced by incubating A549 cell with each particles for 24 hours in vitro 3. Apoptotic alveolar macrophage was observed the findings of zeiosis (membrane blebbing), condensation of nuclear chromosome and many vacuoles in cytoplasm, electomicroscopically.