OBJECTIVETo clarify the dose-response relationship between asbestos dust exposure and lung cancer incidence in chrysotile asbestos miners by fixed cohort study and to investigate the incidence rates of lung cancer in exposure to different concentrations of asbestos dust.

METHODSA retrospective cohort study was conducted in 1932 asbestos miners who registered from January 1, 1981 to December 31, 1988, had worked for at least 1 year, and had no obvious cardiopulmonary diseases; the cohort study began in July 2009 and covered a time span of 29 years (1981 - 2009). The personal information, occupational history, disease history, and health data of these miners were recorded, and the monitoring data on dust concentrations in the mine over the years were collected. The dose-response relationship between asbestos dust concentration and lung cancer incidence was established by the method of life table; a regression equation was fitted to predict the excess incidence rates of lung cancer under the conditions of different working years and dust concentrations.

RESULTSA significant dose-response relationship was observed between cumulative exposure (Ce) and cumulative probability (Px) of lung cancer incidence, and the smokers hada higher Px than nonsmokers. When Ce was less than 2000 mg/m(3)·each year, Px reached 6.58/10000; when Ce was not less than 2000 mg/m(3)·and less than 3000 mg/m(3)·each year, Px reached 91.72/10000; when Ce was more than 5000 mg/m(3)·each year, Px was as high as 141.02/10000. The three models were fitted to obtain the optimal regression equation: Px = -0.0004Ce(2) + 0.0052Ce - 0.0011 (r(2) = 0.9387). In the workshop of asbestos mine in this study, the average dust concentration was 85 times higher than the limit in 2009, so the excess incidence rate of lung cancer was 112.598/10000 if the miners worked under this condition for 40 years, according to the equation.

CONCLUSIONThere is a significant dose-response relationship between cumulative asbestos exposure and lung cancer incidence in chrysotile asbestos miners. The risk for lung cancer rises as asbestos exposure increases.

Asbestos, Serpentine ; toxicity ; Dust ; Female ; Humans ; Lung Neoplasms ; etiology ; Male ; Mining ; Occupational Exposure ; Retrospective Studies

OBJECTIVETo study the effects of aluminum citrate (AC), rare earth compounds (REC) and sodium selenite (SS) on the surface elements of chrysotile fibers and the inhibitory mechanisms of three compounds for chrysotile-induced biological activities.

METHODSAfter being soaked in 250, 500 and 1000 microg/ml aluminum citrate solutions, 125, 250, 500 and 1000 microg/ml mixed rare earths solutions or 125, 250, 500 and 1000 microg/ml sodium selenite solutions for 10 min or 1 hour, the fabrication and the levels of surface elements of chrysotile fibers were determined.

RESULTSAluminum citrate, mixed rare earths or sodium selenite all could be adsorbed by chrysotile fibers. After pretreatment of chrysotile fibers with aluminum citrate, mixed rare earths or sodium selenite solutions for 10 min or 1 hour, the corresponding elements or ion on the surface of chrysotile fibers increased with the increase of concentration of the solutions.

CONCLUSIONPretreatment of chrysotile with aluminum citrate, mixed rare earths or sodium selenite solutions can change the fabrication and the levels of surface elements of chrysotile fibers, and inhibit the biological activities of chrysotile by "sealing" some "active sites" on the surface of chrysotile fibers.

Asbestos, Serpentine ; chemistry ; toxicity ; Citric Acid ; chemistry ; Metals, Rare Earth ; chemistry ; Sodium Selenite ; chemistry

OBJECTIVETo study the cytotoxicity induced by chrysotile asbestos (CA), rock wool (RW) and wollastonite (WS).

METHODSV79 cells were divided into 4 groups. i.e. CA group, WS group, RW group and control group (200 microl PBS). The exposure concentration of dusts was 100 mg/L, The cell viability was detected by MTT and lactate dehydrogenase (LDH) activity assays. The technique of scanning electron microscopy was used to examine the change of V79 cells.

RESULTSSiO2 was main constituent for 3 kinds of dusts. In MTT assay, the cell viability of RW and WS groups was 64.8% and 65.7%, respectively, which were significantly higher than that (54.5%) of CA group (P < 0.01). In LDH assay, the LDH activity of RW and WS groups [(15.7 +/- 50.9), (12.3 +/- 3.7) U/L, respectively] was significantly lower than that [(20.2 +/- 0.9) U/L] of CA group (P < 0.05). In scanning electron microscopy examination, it was found that the two ends of V79 cells in CA group contained a great deal of fibers remaining bodies, but the V79 cell appearance in RW and WS groups was normal.

CONCLUSIONThe cytotoxicity induced by RW and WS is significantly lower than that induced by CA for V79 cell.

Animals ; Asbestos, Serpentine ; toxicity ; Calcium Compounds ; toxicity ; Cell Line ; drug effects ; Cricetinae ; Cytotoxins ; toxicity ; Lactate Dehydrogenases ; metabolism ; Mineral Fibers ; toxicity ; Silicates ; toxicity

OBJECTIVETo investigate the apoptosis rate and the reactive oxygen species (ROS) level induced by chrysotile fibers in BEAS-2B cells and the blockage effect of free radical scavengers on the induction of chrysotile fibers.

METHODSThe cell survival rate, the morphological variation of BEAS-2B cells, the apoptosis rate, the expression levels of gene caspase-3 and the ROS generation level were measured by using trypan blue phagocytosis, hematoxylin and eosin staining, oligonucleosomal DNA fragmentation assay, FCM, RT-PCR and fluorescent probe DCFH-DA in the suspension (0, 5, 10, 20, 100 and 200 microg/cm(2)) and the filtrate (0, 100, 200, 400, 800 and 1600 microg/ml) of chrysotile fibers. Addition of free radical scavengers such as catalase, dimethyl sulfoxide and mannitol prevented the radical generation and gene expression.

RESULTSSurvival rates of BEAS2B cells treated by the suspension (0, 5 and 10 microg/cm(2)) and the filtrate (0, 100 and 200 microg/ml) of chrysotile fibers for 24 hours were above 90%. The apoptotic rates of BEAS-2B were increased with the concentration of suspension and filtrate from chrysotile fibers (P < 0.05). Otherwise, caspase-3 mRNA and ROS were stimulated by chrysotile fibers. Free radical scavengers such as CAT, DMSO and mannitol could reduce these stimulations. The ROS blocking rate of suspension of chrysotile fibers was 23.7%, 21.6% and 11.2% respectively, and that of filtrate was 37.9%, 40.3% and 10.6% respectively.

CONCLUSIONApoptosis is induced in BEAS-2B cells exposed to chrysotile fibers suspension and filtrate. Generation of ROS plays an important role in chrysotile fibers-induced BEAS-2B cell apoptosis.

Apoptosis ; drug effects ; Asbestos, Serpentine ; toxicity ; Cell Line ; Drug Antagonism ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Free Radical Scavengers ; pharmacology ; Humans ; Oxidative Stress ; Reactive Oxygen Species ; metabolism

OBJECTIVETo study the effects of chrysotile on the activities of some enzymes for xenobiotics metabolism.

METHODSUICC chrysotile (UC) and China Mangya chrysotile (MC) asbestos fibers were used at different doses (0, 25, 50, 100, 200 mg/L) to study its effects on the activities of cytochrome P4501A1 and glutathione S-transferase (GST) in A549 cell line. Also, the effects of chrysotile on the activities of CYP1A1 and GST induced by benzo(a)pyrene were studied.

RESULTSThe activity of EROD increased slowly with the increasing dose of UC, as A549 cells were incubated with UC for 24 h, and EROD activity increased by 40% at a dose of 200 mg/L UC. However, activity of EROD decreased by 32% with 48 h incubation at the same dose, indicating that lower dose of UC and short time could induce the activity of EROD in A549 cells, whereas higher doses and long time could inhibit its activity. MC exhibited a multiphasic effects on the activity of EROD, whether at a dose of 25 mg/L for 24 h or 48 h all gave the strongest induction, 1.86 times or 1.28 times as controls, respectively. However, EROD activity decreased with the increases in MC doses and incubation time, with the lowest as 35% of the controls. The effect of UC on GST activity was not so obvious, with the highest as the increase in its activity by 20%. The highest induction of MC to GST activity was at a dose of 25 mg/L, 2, 5 times as that in controls. With the increases in its doses, effects of MC on GTS activity became inhibition from induction, like that on EROD activity. MC at a dose of 200 mg/L could lower the activity of GST by 18.7%. A549 cells were incubated with chrysotile fiber for 24 h firstly, and then incubated with benzo(a)pyrene to induce the activities of EROD and GST. The results showed that neither UC nor MC could affect the activity of EROD induced by benzo(a)pyrene. However, UC at a dose of 200 mg/L and MC at 100 mg/L could increase the activity of GST induced by benzo(a)pyrene.

CONCLUSIONChrysotile at different doses or its different types showed varied effects on the activities of EROD and GST in A549 cell lines, probably because of different physicochemical characteristics and surface activity of two kinds of asbestos.

Asbestos, Serpentine ; toxicity ; Cytochrome P-450 CYP1A1 ; metabolism ; Dose-Response Relationship, Drug ; Enzyme Induction ; Glutathione Transferase ; metabolism ; Humans ; Lung Neoplasms ; enzymology ; Tumor Cells, Cultured

OBJECTIVETo explore the role of telomerase in asbestos dust induced malignant transformation of human embryonic lung fibroblasts in vitro.

METHODSHuman telomerase catalytic subunit (hTERT) was transferred into human embryonic lung fibroblasts (HELF). Chrysotile dust at concentration of 2.5 microg/cm(2) was added to HELF transduced with and without hTERT (HELF-T+), respectively, and their transduced foci were separated. Biological characteristics of the cells, telomerase activity, length of telomere and cell growth curve were observed. Colony forming test was performed on soft agar to evaluate the nature of transformation.

RESULTSThe hTERT gene was transferred into HELF steadily, and HELF-T+ was established. Malignant transformation occurred in both HELF and HELF-T+ by asbestos stimulation. Asbestos dusts could induce higher rate of transformations in HELF-T+ [(2.08 +/- 1.08)/utensil] than in HELF [(1.08 +/- 0.10)/utensil], P < 0.05. Telomerase activity in both transformed malignant cells and HELF-T+ was higher, as well as the longer length of telomere in them.

CONCLUSIONRate of malignant transformation in cells with more activity of telomerase and longer length of the telomere was higher after stimulation with asbestos, indicating telomerase could play an important role in asbestos induced human cells malignant transformation.

Asbestos, Serpentine ; toxicity ; Cell Transformation, Neoplastic ; drug effects ; Cells, Cultured ; DNA-Binding Proteins ; Embryo, Mammalian ; Fibroblasts ; pathology ; Gene Transfer Techniques ; Humans ; Lung ; pathology ; Telomerase ; genetics ; metabolism

The present review summarizes the results of several follow-up studies assessing an asbestos product manufacturing plant in Chongqing, China, and discusses three controversial issues related to the carcinogenicity of asbestos. The first issue is the amphibole hypothesis, which asserts that the carcinogenicity of asbestos is limited to amphiboles, such as crocidolite, but not serpentines, such as chrysotile. However, considering the possible multiple component of asbestos carcinogenicity in the presence of tobacco smoke or other carcinogens, chrysotile cannot be regarded as non-carcinogenic. Additionally, in a practical sense, it is not possible to assume "pure" chrysotile due to its ubiquitous contamination with tremolite, which is a type of amphibole. Thus, as the International Agency for Research on Cancer (IARC) assessed, all forms of asbestos including chrysotile should be regarded carcinogenic to humans (Group 1). The second issue is the chrysotile/tremolite paradox, which is a phenomenon involving predominant levels of tremolite in the lung tissues of individuals who worked in locations with negligible levels of tremolite due to the exclusive use of chrysotile. Four possible mechanisms to explain this paradox have been proposed but this phenomenon does not support the claim that amphibole is inert. The final issue discussed is the textile mystery, i.e., the higher incidence of cancer in asbestos textile plants compared to asbestos mines where the same asbestos was produced and the exposure levels were comparable. This phenomenon was first reported in North America followed by UK and then in the present observations from China. Previously, levels of fiber exposure were calculated using a universal converting coefficient to estimate the mass concentration versus fiber concentration. However, parallel measurements of fiber and mass concentrations in the workplace and exposed air indicated that there are wide variations in the fiber/mass ratio, which unjustifies the universal conversion. It is possible that contamination by airborne non-fibrous particles in mines with mass fiber conversion led to the overestimation of fiber concentrations and resulted in the textile mystery. Although the use and manufacturing of asbestos has been banned in Japan, more than 10 million tons of asbestos had been imported and the majority remains in existing buildings. Thus, efforts to control asbestos exposure should be continued.
Asbestos ; classification ; toxicity ; Asbestos, Amphibole ; toxicity ; Asbestos, Serpentine ; toxicity ; Carcinogens ; China ; Follow-Up Studies ; Humans ; Lung Neoplasms ; chemically induced ; epidemiology ; Manufacturing and Industrial Facilities ; statistics & numerical data ; Mining ; statistics & numerical data ; Occupational Diseases ; epidemiology ; Occupational Exposure ; adverse effects ; Textiles ; Tobacco Smoking ; epidemiology

OBJECTIVE: This study evaluated the CT characteristics of pleural plaques in asbestos-exposed individuals and compared occupational versus environmental exposure groups. MATERIALS AND METHODS: This study enrolled 181 subjects with occupational exposure and 98 with environmental exposure from chrysotile asbestos mines, who had pleural plaques confirmed by a chest CT. The CT scans were analyzed for morphological characteristics, the number and distribution of pleural plaques and combined pulmonary fibrosis. Furthermore, the CT findings were compared between the occupational and environmental exposure groups. RESULTS: Concerning the 279 subjects, the pleural plaques were single in 2.2% and unilateral in 3.6%, and showed variable widths (range, 1-20 mm; mean, 5.4 +/- 2.7 mm) and lengths (5-310 mm; 72.6 +/- 54.8 mm). The chest wall was the most commonly involved (98.6%), with an upper predominance on the ventral side (upper, 77.8% vs. lower, 55.9%, p < 0.001) and a lower predominance on the dorsal side (upper, 74.9% vs. lower, 91.8%, p = 0.02). Diaphragmatic involvement (78.1%) showed a right-side predominance (right, 73.8% vs. left, 55.6%, p < 0.001), whereas mediastinal plaques (42.7%) were more frequent on the left (right, 17.6% vs. left, 39.4%, p < 0.001). The extent and maximum length of plaques, and presence and severity of combined asbestosis, were significantly higher in the occupational exposure group (p < 0.05). CONCLUSION: Pleural plaques in asbestos-exposed individuals are variable in number and size; and show a predominant distribution in the upper ventral and lower dorsal chest walls, right diaphragm, and left mediastinum. Asbestos mine workers have a higher extent of plaques and pulmonary fibrosis versus environmentally exposed individuals.
Adult ; Aged ; Aged, 80 and over ; Asbestos, Serpentine/*toxicity ; Asbestosis/*etiology/radiography ; Asian Continental Ancestry Group ; Environmental Pollutants/toxicity ; Female ; Humans ; Male ; Middle Aged ; Mining ; Occupational Exposure ; Pleural Diseases/*etiology/radiography ; Republic of Korea ; Tomography, X-Ray Computed

OBJECTIVETo investigate whether asbestosis is a risk factor for mortality of lung cancer.

METHODSA fixed cohort study was established in an asbestos plant in Chongqing, China, and followed up for 30 years from the beginning of 1972. Basic personal information on life state, cause of death, and diagnosis of asbestosis was collected. Multiple logistic regressions were applied to analyze risk factors.

RESULTSDuring the 30-year follow-up, 584 male workers constituting a total of 14,664 person-years were monitored and data were analyzed. Among them, 203 (34.8%) died and the mortality rate was 13.8 per 1000 person-years, cancer accounting for 37.4%. Excess risks were observed for lung cancer (OR = 3.72) and nonmalignant respiratory diseases (OR = 2.73) among workers with asbestosis. High-exposure level was another risk factor for lung cancer (OR = 3.20). Workers with category II of asbestosis demonstrated a higher OR of both lung cancer and nonmalignant respiratory diseases than those with category I of asbestosis.

CONCLUSIONHigh asbestos exposure level and asbestosis were the risk factors for death of lung cancer and nonmalignant respiratory diseases. Asbestosis is an independent risk factor for lung cancer among Chinese workers exposed to chrysotile, the risk increases with the increasing profusion of opacities of lung.

Adult ; Air Pollutants, Occupational ; toxicity ; Asbestos, Serpentine ; toxicity ; Asbestosis ; complications ; mortality ; Chemical Industry ; China ; epidemiology ; Humans ; Lung Neoplasms ; chemically induced ; mortality ; Male ; Occupational Diseases ; chemically induced ; mortality ; Occupational Exposure ; adverse effects ; Odds Ratio ; Risk Factors