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A combination of the needs of business, employee desires and safety and health considerations is stimulating increasing attention to the time spent by people at work and the timing of that work. Particularly we are seeing: - innovative work schedules for 24-hour mining businesses; and - response from industry to accommodate the needs, even the desires, of employees in return for systems which are more productive and more capital efficient. There appears to be an evolutionary trend for business management to become more sophisticated and responsive to the need for achieving close to best cost work schedules to sustain continuous improvement. The underlying motivating forces driving this trend for improved techniques in organising attendance at, and time spent at work, is the seemingly inseparable combination of technological advance and ever-increasing accumulation of capital. The mining industry has not remained untouched by this thrust for ever-increasing need for best use of labour, to adopt advances in technology and to provide attractive opportunities for putting accumulated capital to work. An essential component of this on-going thrust is a substantial effort by the mining industry to improve the performance of labour by providing most-productive work schedules.

Jan 1, 1996

By Vladimir J. Ovdenko, Sergey N. Lazarenko, Evgeny L. Schastlivtsev

The term sustainable development shortly appeared in international use in the run of UNO Environmental Protection Conference held in Rio de Janeim in 1992, bears the concept, that evolution process ( associated either with a region or society) should provide mutual interests concern in three aspects - environmental, economic and social ones, admitting as well the fact , that environmental protection should become an integral part of each process and cannot be regarded separately. In this connection it seems quite reasonable to employ the principal of sustainable development, while creating the model of industrial mastering the territory constraint lands viewing their future, for a example, in rich mineral deposit's development. In Kuznetsk coal basin in Russia ( west Siberia) the development of a big coal deposit Erunakovsky is now being underway. The major part of coal will be mined with open cast method, resulting the number of local environmental adverse impacts' occurrence. In such a situation mastering of sustainable development model is given the top priority, demonstrating the essential result of its application in a form of possibility to define the best correlation between economically expedient and environmentally tolerable loads during coal mining. The given paper is an attempt to work out the main principals to approach the creation of sustainable development model in regard of the definite region case. To simplify the presentation of employed approach's main idea, the given below accepts as its component only one of many actually existing environmental profiles, that define mining pro- cess impact on environmental situation -the size of infringed (de- graded) lithosphere surface. Basically, the actually existed correlation between spheres. grounding the model of sustainable development - economic, environmental and social- is given in a form of nomogram under Fig.1. On the presented graph the prognostic values of broken lands relative extent within Erunakovsky boundary ( to be compared with total region area taken as 100%) are arranged on axis x". Axis "y- demonstrates the main values associated with complete economic background, making the intrinsic part of the principal for sustainable development, i.e. annual coal output for the given area. It's top, used in assessment value relates to actual showings implied for the study region project and quantifies 60 min. tons. While regarding the social facet of principal for sustainable development, the applied mode to separate social issues into two types - one profiling a welfare standard of living and the other. pertaining the way environmental situation contributes to the degree of &ologica-1 comfort in people's living was defined as the most expedient and the most adequate in the matter of reflecting the actual terms of vital activity of the society. In accordance with the cited above the economic level showings are plotted on the graph on "-x” axis, while "-y" one obtains the values associated with the point of ecological comfort presented in conventional units. For the maximum possible conventional point of living (corresponding in nomogram to 1.0 value) a welfare level secured with industrial region economic activity revenue was assumed in case the top planned annual amount of coal is delivered ( 60 min. tons). While studying the index of public economic welfare, environmental conditions corresponding level in its original state i.e. prior to any industrial work carried in the region, was adopted as its top possible conventional rating (1.0). The given nomogram displays the integrity of x-f(y) type interrelations plotted on the basis of four separate dependencies, precisely a) the size (area) of infringed earth's surface as a function of coal output in the region; b) subordination of ecological comfort of people's living to the degree of lands infringement; c) interconnection of economic and environmental components of people living; d) interconnection of economic level of people's living and the amount of coal mined in the region. Linked to a single unit, these separate plain dependencies create, as seen from the graph, a more intricate system of bonds, that affords during defining or changing this or that system parameter to secure undergoing changes, that occur to other parameters of the system. The mentioned reason made it possible to consider and drive to mutual conformity ( as far as it is possible) all parameters values for the defined system's relations, that in their turn indicate the concern of other aspects of a sustainable development principal. According to the graph, in order to get not more than 50% of infringed land left after the deposit's mining, it is advisable to ex- tract not more than 40 min. tons of coal annually, gaining in this case the level of ecological comfort for living in the amount of not

Jan 1, 1996

By J. P. Bellot

During the non-ferrous metal processing, the melting step under vacuum or under rarefied gas leads to volatile metal losses. It is the case of the metallurgical processing of the nickel-based, titanium-based or zirconium-based alloys where the evaporation losses don't allow a sufficient control of the alloy chemical composition. A theoretical approach has been carried out involving both a continuum description in the liquid phase and a molecular approach in the rarefied gas phase. The finite volume method is used in order to solve the coupled transport equationsin the liquid, whereas the Boltzmann equation is modelled by using a Monte Carlo method. At the liquid metal and metallic vapor interface, the volatilization and recondensation fluxes link up the two calculations. Simulation results are given for the melting and refining of reactive metals such as titanium alloys where the control of the chemical composition remains a major difficulty. The validity of the kinetic Langmuir's law is discussed for different operating conditions.

Jan 1, 1996

Diversity; what a wonderful topic. Diversity; the condition or quality of being diverse, different, varied to the point that the very word diversity means different things to different people. As one example of diversity the American Science Magazine (April, 1994) contained a light-hearted interview with Dr Noitall who was pushing his case for diversity.

Jan 1, 1996

By J. A. Murray

Maintaining satisfactory air quality in electro-winning tankhouses has been problematic and costly, particularly as plant operating current densities have increased. Conventional approaches, including the use of beads, hollow spheres, surfactants and coalescer devices, have not proved completely effective, requiring that powerful ventilation systems be installed. As workplace and environmental regulations become more stringent, containment of the acid mist at its source is more attractive. An electrode cap system based on this approach has been developed and tested in two commercial copper electrowinning tankhouses. The design, development, installation and cost of the new electrode cap system are described.

Jan 1, 1996

By R. Hogg, Y. Lee, D. E. Rannels

"Lee, Yu-Chen, Richard Hogg, and D. Eugene Rannels. Extracellular matrix synthesis by coal dust-exposed type II epithelial cells. Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L365–L374, 1994.—Although integrity of the alveolar basement membrane may influence progression of lung injury induced by inhaled particulates, little is known about direct effects of coal dusts on the alveolar epithelium or its extracellu¬lar matrix (ECM). Effects of dust on synthesis of cell and ECM proteins by type II cells (T2P) was thus investigated. Three coal dusts (anthracite no. 867; bituminous no. 1451 and no. 1361) and mine dust MIT-3, of respirable size, were studied as a function of dose and time over 3 days of primary T2P culture. On day 1, 750 µg/ml of 867 were required to increase relative synthesis of ECM proteins (ECM/cell). MIT-3, 1451, and 1361 were without effect. By day 3, 867 or MIT-3 increased ECM/ cell 60-100% at 300 µg/ml; 1451 produced modest, dose-dependent stimulation, whereas 1361 remained without effect. None of the dusts caused significant cytotoxicity. The results show dose- and time-dependent effects of well-characterized coal and mine dusts to modify partitioning of newly synthesized proteins into the ECM and suggest that coal dust exposure may modulate structure or function of the subepithelial basement membrane.basement membrane; cell culture; inorganic dust; lung injury; extracellular matrix deposition; pulmonary epitheliumCHRONIC EXPOSURE to coal dust may be associated with development of pulmonary fibrosis and consequent loss of normal lung function (see Ref. 26 for review). Al¬though the pathways of inorganic dust-induced lung injury are recognized to involve an inflammatory re¬sponse, the underlying pathogenic mechanisms are not understood in detail. Acute and chronic responses to dust exposure involve a variety of interacting cells of the immune system, including macrophages, T cells, and B cells, along with pulmonary fibroblasts. These responses reflect direct effects of the dust particles, as well as indirect effects mediated by soluble factors, including cytokines and eicosanoids (see Ref. 41 for review).Studies of pulmonary macrophages and fibroblasts following silica exposure suggest that dust-induced damage at the airway surface may involve cellular injury through oxidant-mediated pathways. Coal dusts and related inorganic particulates can activate the alveolar macrophage (42) to produce fibronectin (15) and cytokines, such as interleukin-1 or tumor necrosis factor (4) and/or other soluble products which act locally (29) to cause acute cellular injury and to initiate the progression of fibrotic lung damage (16). Type I epithelial cells are typically more susceptible than type II cells to oxidant injury. Type I cell damage and subsequent death leads to denudation of the subepithelial basement membrane (2, 21) and can be associated with leakage of plasma constituents from the pulmonary vasculature into the alveolar compartment (13)."

Dec 1, 1995

By R. K. Dunham, D. J. Reddish, X. L. Yao

Paper presented at the conference: Risk assessment in the extractive industries, held in Exeter, UK, 23-24 March 1994, and first published London: IMM, 1994, preprint volume, 10pp., 10 refs. The integrated approach combines a powerful ground movement prediction program with a knowledge-based expert system. ESDAS (Expert Structural Damage Assessment System) was developed to evaluate mining subsidence damage in the form of risk and in terms of the three vital contributing components (mining factors, site factors and structural factors). Using a certainty factor risk assessment technique, the system can be used to predict the likely damage to a particular structure subjected to mining subsidence. A previously developed powerful ground movement prediction program, SWIFT (Subsidence With Influence Function Techniques), has been combined with the expert system to allow the mining factor to be more accurately determined in a broader range of mining layout. Since SWIFT can be calibrated to any particular coal field using local subsidence data, it is believed that the integrated system could be used in any coal field worldwide for the assessment and control of mining subsidence damage risks

Dec 1, 1995

By S. R. Rannels, D. E. Rannels

"I. IntroductionThe alveolar surface of the lung is covered by two populations of pneumocytes, type I and type II epithelium. The type I cell, which accounts for most of the alveolar surface area and provides a highly specialized barrier for gas exchange (Rannels et al., 1991), is poorly understood. Although approaches to type I cell purification have been discussed, they have not been applied widely because of the lack of phenotypic markers to monitor isolation procedures (Dobbs et al., 1988; Danto et al., 1992). In contrast, the type II cell has been studied extensively, largely because of the development of reliable procedures for its isolation and primary culture. Investigations based on the use of purified populations of cultured type II cells have provided convincing evidence to support a role for the pneumocytes both in the maintenance of normal lung function and in the response of the lung to injury (for review, see Rannels and Rannels, 1989).While type II cells can be isolated by a variety of approaches, the protocols used most commonly are modifications of the gradient method of Dobbs and Mason (1979) or of the panning method of Dobbs et al. (1986). Purification of the cells based on density gradient centrifugation is reliable and consistent, with yields of 30 to 40 X 106 type II cells per rat of 230 g body weight. Isolation procedures applied to a minimum of three to four rats provide the best results, as lower cell yields are common with the use of fewer animals. The protocol below is designed to obtain a maximal cell yield from the lungs of six rats.II. Materials and InstrumentationMaterialsCalbiochem: DNase I (Cat. No. 260912); Corning: culture flask, 75 cm2 #25115; Costar: culture plate, 24-well #3424; disposable serological pipette #4101; Elastin Products Inc: elastase #E-134; Falcon: cellulose nitrate membrane filter, 0.22 µm, #7105; conical tube, 50 ml, #2070; culture dish, 100 mm, #3003; culture plate, sixwell, #3046; Fisher: BaS04 , #B68-500; NaCl, #5271-3; NaHC03 , #5233-50; Fort Dodge Laboratories: pentobarbital, #1206-lE; Gibco: Dulbecco's minimal essential medium (DMEM), #430-1600EC; Hanks' balanced salt solution (HBSS), #310- 4185AG; Joklik's modified Eagle's medium (JMEM), #410-2300EC; HyClone Laboratories Inc: fetal calf serum (FCS ), # A-1115-L; I CN Biochemicals (Flow Labora tories): amphotericin B, #16-723-48; newborn calf serum (NCS), #29-121-54; try pan blue, # 19 5 5 32; Na/gene: Erlenmeyer flask, # 100-4116C; Pharmacia: Percoll, #17-0891-01; density marker beads, #17-0549-01; Sigma: gentam1cm sulfate, #G3632; penicillin/streptomycin, #P3539; trypsin inhibitor, #T9128; Tetko: HC- 160 nylon mesh, #3-160-53."

Dec 1, 1995

By R. D. Dey, V. Castranova, J. M. Antonini, J. A. Blackford Jr.

Alveolar macrophages (AM) exposed to cytokines or bacterial lipopolysaccharide (LPS) produce the free radical nitric oxide (NO·) by an inducible nitric oxide synthase (iNOS). They also release reactive oxygen free radicals following exposure to silica dust. The purpose of the present study was to determine whether NO· is produced by rat AM and/or recruited leukocytes following the intratracheal (IT) instillation of silica. Male Sprague-Dawley rats (175 to 225 g) were IT instilled with either silica dust (10 mg/100 g body wt) or LPS (0.25 mg/100 g body wt). After 24 h, bronchoalveolar lavage cells (BALC) and lavaged lung tissue were assayed for iNOS mRNA. Cell counts of BALC and iNOS-dependent (Nw-nitro-Larginine methyl ester [L-NAME]-inhibitable) chemiluminescence generated by AM were also determined. Northern blot analysis demonstrated that the steady-state levels of BALC iNOS mRNA were significantly increased by 3-fold following IT silica and by 7-fold following IT LPS. Partially enriched fractions of either AM or leukocytes from silica-treated rats both exhibited significantly elevated iNOS mRNA in Northern analysis. iNOS-dependent chemiluminescence was significantly increased in AM by 36-fold following IT silica and by 89-fold following IT LPS. Differential counts of BALC showed that AM numbers did not change in any of the treatments; however, red blood cells increased by 30-fold following IT silica and by 23-fold following IT LPS. Total leukocytes (polymorphonuclear leukocytes plus lymphocytes) increased by 58-fold following IT silica and by 274-fold following IT LPS. The results demonstrate that AM and neutrophils iNOS steady-state mRNA levels, AM iNOS-dependent chemiluminescence, and lavagable red blood cells and leukocytes all increased following IT silica. These findings suggest that NO· production in rat AM and neutrophils is increased in response to silica. NO· has the ability to then combine with superoxide and form a highly reactive toxic species, peroxynitrite, which may be responsible in part for silica-induced lung damage.

Dec 1, 1995

By E. Niehuis, J. Y. Kim, H. G. Cramer, S. L. Chryssoulis, K. G. Stowe, C. Bendel

TOF-SIMS was used to detect, identify from parent molecular ions and determine the relative concentrations of collectors sorbed on the surface of mineral particles in concentrate and tailings samples from three Canadian concentrators. In the Kidd Creek Zn circuit, sphalerite lost to tailings carried on average a quarter of the amount of isobutyl xanthate present on that recovered to Zn concentrate; amyl xanthate, which is not reported as added to the circuit, was also detected on floated sphalerite and pyrite. At Brunswick, sphalerite particles lost to the scavenger tailings had ten times less amyl xanthate and isobutyl xanthate than those recovered to the Zn final concentrate, while both xanthates were detected on sphalerite floated to the Cu-Pb cleaner circuit. At Matagami, significantly more isopropyl xanthate and isopropyl dithiophosphate were detected on sphalerite recovered to the final Zn concentrate than on that lost to the Zn rougher tailings

Dec 1, 1995

By S. P. Ball, A. J. Monhemius

In a laboratory study under acidic oxidising conditions, the thiocyanate system gave results at least as good as cyanide and considerably better than thiourea, with modest consumption of SCN (less than 1 kg/t ore). For both cyanide and thiocyanate lixiviants a residence time of about 24 h was required for maximum gold extraction, which was generally in the range of 92-96%. The adsorption of gold from thiocyanate leach liquors was found to be rapid, but activated carbon catalyses the autoreduction of ferric iron to ferrous iron in thiocyanate solutions, suggesting that ion exchange may be a better recovery route

Dec 1, 1995

By D. G. Leddy, J. B. Johnson, L. D. Gratz, S. T. Bagley

"Studies have been conducted at Michigan Technological University (MTU) for over twenty years on methods for characterizing and controlling particulate emissions from heavy-duty diesel engines and die resulting effects on regulated and unregulated emissions. During that time, control technologies have developed in response to more stringent EPA standards for diesel emissions. This paper is a review of: 1) modem emission control technologies, 2) emissions sampling and chemical, physical and biological characterization methods and 3) summary results from recent studies conducted al MTU on heavy-duty diesel engines with a trap and an oxidation catalytic converter (OCC) operated on three different fuels. Control technology developments discussed are particulate traps, catalysts, advances in engine design, the application of exhaust gas recirculation (EGR) and modifications of fuel formulations. Methods for dilution tunnel sampling, particle size analysis, chemical analysis with emphasis on polynuclear aromatic hydrocarbons (PAH) and nitro-PAH, and biological characterization using mutagenic activity (Ames) assays are described, along with statistical approaches to experimental design and data analysis.In studies at MTU, both particulate traps and an OCC have been shown to be effective for the reduction of total particulate mauer (TPM), with the OCC being better al reducing all forms of hydrocarbon emissions, including PAH and nitro-PAH, and with the traps being better at removing the solids (SOL). The use of low sulfur fuel (0.Ql % by mass) has led to additional reductions in TPM; the low sulfur fuel has been shown to reduce the number of small, nuclei-mode particles for one of the engines tested. PAH, nitro-PAH, and mutagenic actively levels generally decreased with use of either the traps or the OCC.INTRODUCTIONDuring the 1980s and the early 1990s there have been significant advancements in the development of technology to control diesel particulate emissions. Efforts have been focused on internal control of the engine by design, the use of after-treatment devices, and improvements in fuel formulations to reduce all the diesel emissions. The research and development activities have been driven by the need to meet the US EPA heavy-duty vehicle standards shown in Table 1. The important standards for new technology are the 1994 heavy-duty vehicle 0.1 gm/bhp-hr particulate, the new urban bus 0.05 gm/bhp-hr particulate standard for 1996 and the heavy-duty vehicle 4.0 gm/bhp-hr NOx standard for 1998."

Dec 1, 1995

By W. P. C. Duyvesteyn, B. J. Sabacky

Reprinted with revisions from Extractive metallurgy of copper, nickel and cobalt, volume I: Fundamental aspects. ed. Reddy R.G., Weizenbach R.N. Warrendale, Pennsylvania: The Minerals, Metals and Materials Society, 1993. Development work on the Escondida process, concluding with the successful operation of an integrated leach-SX-EW pilot plant and a pilot flotation plant for the upgrading of leach residues, demonstrated that all major process objectives could be achieved. Extraction of 40% of copper in concentrates containing monovalent copper was achieved with essentially no oxidation of sulphide sulphur. The Cu contents of leach residues from four different types of concentrate were successfully upgraded to the original feed grades, giving a product that has potential as a high-quality concentrate for the smelter market. A compact solvent extraction section effectively recovered the ammonia lixiviant for recycling to leaching and selectively transferred Cu into a conventional acid sulphate electrowinning system. High-quality "six-nines" copper cathode was produced on commercial-scale stainless steel blanks, demonstrating that the process will be able to compete effectively in the premium cathode market

Dec 1, 1995

By I. Marklund, W. Hustrulid

Sublevel caving is likely to remain the dominant system at both Malmberget and Kiruna for the foreseeable future. The sub-level interval has increased from 12 m in 1983 to 30 m, requiring more effective drifting and the development of a contour blasting technique to reduce requirements for rock reinforcement. Production drilling is mainly by hydraulic hammers or water-powered in-the-hole machines drilling 115 m diameter holes. Loading operations are undertaken 7 days/week with 15-25 tonne capacity electric shovels. Production has increased by nearly 70% since 1983 and productivity has risen threefold

Dec 1, 1995

By S. L. Weber, D. E. Banks

"Silicosis was first reported by the ancient Greeks and is apparently as old as human history. The prevalence of this illness peaked in the last half of the 19th century and the early part of this century, when mechanized industry was developing and the relationship between dust exposure and disease was less well understood. Yet, even today in devel-oped countries, sporadic outbreaks of silicosis occur when workers are consistently exposed to silica particles of respir-able size (0.5 to 5.0 µm in diameter) at levels exceeding those recognized to be safe.Silicon dioxide or silica. is the earth's most abundant mineral. Silica is considered to be either free (i.e.. unbound to other minerals) or combined. Minerals with high amounts of free silica include quartz (including granite) flint. Chert, opal, chalcedony, and diatomite. Combined forms of silica are called silicates and include, among others, asbestos talc and kaolin.In the crystalline form, silica exists as quartz, cristobalite, and tridymite (Fig. 28). Of these quartz is ubiquitous in the environment and occurs as sand and as a part of many rocks. Cristobalite and tridymite occur naturally in lava and can be formed by the heating of quartz or amorphous silica. Cristo-balite is more tibrogenic than quartz. Amorphous silica is noncrystalline and, therefore, is relatively nontoxic and does not cause silicosis. It occurs as diatomite (skeletons of pre-historic marine organisms) or as vitreous silica (glass), the result of carefully melting and then quickly cooling free crystalline silica. Heating diatomite with or without alkali (a process known as calcining), forms cristobalite and adds the respiratory toxicity of free crystalline silica.There are many opportunities for occupational exposure to respirable crystalline free silica. Some of the commonly en-countered occupations in which the risk of silicosis exists are reported in Table 20.Silicosis. the pulmonary disease caused by the inhalation of silica particles of respirable size, is most commonly cate-gorized by findings on the chest radiograph. The most typical presentations simple silicosis and progressive massive fibrosis appear different radiologically but are grouped under the category of classic silicosis because they are a part of the radiographic spectrum of this illness. Radiographically, simple silicosis appears as small (less than 10 mm in diameter), rounded opacities, typically predominant in the upper lung zones. Progressive massive fibrosis is the result of the coalescence of these small nodular opacities and appears as larger opacities (more than 10 mm in diameter), again typicallydistributed in the upper lung zones."

Dec 1, 1995

By H. K. Taylor, B. Denby, L. D. Smith

Contributions by H.K. Taylor and G.A. Davis discuss the three papers published in Transactions IMM A, vols. 103 and 104, with responses by Smith and Dowd

Dec 1, 1995

By K. Nielsen, J. Kristiansen

A series of laboratory blasting and grinding tests on three types of hard and competent rock (coarse-grained monzonite, fine-grained granite and very fine-grained gabbro) showed that a higher level of applied explosive energy enhanced grindability and produced a larger amount of fine (-0.106 mm) material. This confirmed reported industrial experience and the results of previous investigations. However, the results did not provide any information on the quantitative relationship between the energy applied in primary blasting and that required in subsequent comminution. Only about 1% of energy consumed in conventional grinding is used to create new surfaces, while power efficencies in cone crushers have been estimated at 70-80%. In blasting, up to 20% of explosive energy may be transmitted to the surrounding rock as elastic strain energy, leading to both primary rock breakage and the generation of microcracks

Dec 1, 1995

By S. P. Singh

The purpose of the cut is to provide a free face to which the remainder of a development or breasting round can break. The results of field testing in drifts and at a quarry face were used as a basis for a description of the rock breakage and flushing mechanism in the cut. It was concluded that the important features of a cut design are proper hole spacing, sufficient relief volume, drilling accuracy and relief holes slightly longer than the planned length of the round. The void space provided by the relief holes should be about 15% of the cut volume, with more required in weak, highly fissured rocks. The importance of drilling accuracy increases with round length, an error being magnified by the small blasthole spacing. The first hole pulls only about 20% of the round length, 4-6 holes having to be fired before the cut is pulled close to its design depth. The first four blastholes should be fired with a minimum inter-hole delay of 100 ms to provide progressive relief of burden and avoid the superimposition of ground vibrations. The earliest-firing charge should be closest to the relief area and act laterally, while the first of the vertically-fired charges to be detonated should be the uppermost. Problems during cut-pulling include sympathetic detonation, dynamic pressure desensitisation, charge disruption and freezing of the cut

Dec 1, 1995

By J. A. Finch, D. Lin

The robustness of the large-sections correction procedure, Hill's fast approximation, Barbery's correction and the PARGEN correction was examined by comparing their ability to reconstruct the true liberation distribution using sectioning data from computer-generated spheres. The results indicate that the flexibility of a correction procedure is related to the assumptions it makes about the continuity of the liberation distribution, locked-particle characteristics and ore texture. Overall, the large-sections procedure appeared to be the most generally applicable. The Hill fast approximation performed well, but this was probably because it partially incorporates the sphere model; the performance of the PARGEN and Barbery corrections varied from case to case.

Dec 1, 1995

By S. L. Weber, V. Castranova, D. E. Banks, J. K. H. Ma, Y. Rojanasakul, J. Y. C. Ma, M. Bhat

"The mechanism of bleomycin-induced pulmonary fibrosis is not ye: clear. Recent studies have shown that alveolar macrophages (AM) can be stimulated by bleomycin in vitro releasing inflammatory cytokines, suggesting that the interaction of bleomycin with AM is an important step in the drug-induced fibrotic process. Bleomycin is known to bind DNA and generate oxygen radicals through complexation with Fe2+ and oxygen. To provide,more insight into the cellular oxidative property of bleomycin, v.s have developed a fluoromicroscopic method using 2',7'-dichlorofluorescin diacetate (DCFHDA) as an oxidative fluorescence probe to study the deomycin-induced intracellular oxidation in rat AM and the inhibition of the oxida¬tion by taurine, a compound known to inhibit the bleomycin-induced fibrosis. Bleomycin at 5 to 20 ug/ml has a moderate stimulatory effect (1.87- to 2.66-fold) on the secretion of superoxide anion. A high concentration of bleomycin (20 ug/ml), however, inhibits cell response to zymosan-induced secretion of superoxide anion. At 4 ug/ml, bleomycin has no effect on cell membrane integrity or morphology but results in a significant increase in intracellular oxidation. This oxidative process is Fe2-,-dependent and is accompanied by an increase in intracellular calcium (35 nM). Both the intracellular oxidation and calcium rise induced by internalized bleomycin are inhibited by pretreatment of cells with varying concentrations of taurine (25, 125, and 187.5 uM). The inhibitory effect on intracellular oxidation .vas found to be 36, 57, and 60%, respectively. These results demonstrate a stimulation-inhibition relationship between bleomycin and taurine on re cellular oxidation at a subcytotoxic dose of bleomycin, suggesting that the oxidative effect of the intracellular bleomycin-Fe2 complex is important in the initiation of the fibrotic process. — Environ Health Perspect 102 (Suppl10):91-96 (1994) IntroductionThe pulmonary system is most susceptible to oxygen radical-induced diseases due to its constant exposure to the highest oxygen tension, and the potential encounters with oxidant gases such as ozone, nitrogen oxides, and toxic doses of dust particles. The lung is also a well-perfused organ and thereby vulnerable to the effect of circulating xenobiotics such as paraquat, and, bleomycin, which is known to cause pulmonary injuries (1). Alveolar macrophages (AM), which act as a means of defense by phagocytizing inhaled dust particles and microorganisms while increasing production of reactive oxidative species, have been shown to play an important role in mechanisms leading to oxidative lung injury and fibrosis (2-4)."

Dec 1, 1995