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Biomedical subjects

L C Chen

Publications and source records attributed to L C Chen.

At least 109 records · Page 6Linked to original sources
PubMed1995

Pulmonary effects of the cocaine pyrolysis product, methylecgonidine, in guinea pigs.

The pulmonary effects of the cocaine pyrolysis product, methylecgonidine (MEG; anhydroecgonine methyl ester), were assessed in guinea pigs. Specific airway conductance (SGaw), which decreases during bronchoconstriction, was measured in guinea pigs exposed to atmospheres containing a condensation aerosol of MEG free base (13 +/- 1 mg/liter of air), nebulized MEG fumarate (3 and 12% in phosphate buffered saline) or nebulized acetylcholine chloride (0.2 and 0.4% in phosphate buffered saline). A decrease in SGaw to 24.0 +/- 4.2% (mean +/- 2 S.E.M.) of baseline levels was observed in guinea pigs breathing MEG free base. A decrease to 28.4 +/- 4.5% of baseline was observed following administration of 0.4% acetylcholine. No change in SGaw was measured in guinea pigs exposed to 3% MEG fumarate but SGaw was reduced to 69.3 +/- 5.3% of baseline after exposure to 12% MEG fumarate. MEG free base poses an alkaline challenge to the lung, 3% MEG fumarate is neutral (pH approximately 7.4) and 12% MEG fumarate is acidic (pH approximately 4.3); thus, MEG free-base and 12% MEG fumarate might provoke a reflex bronchoconstriction due to direct pulmonary irritant effects. These results suggest that MEG free base produced during crack pyrolysis may play a role in bronchoconstriction observed in crack smokers.

Animals↗
PubMed1995

Effects of methylecgonidine on acetylcholine-induced bronchoconstriction and indicators of lung injury in guinea pigs.

The fumarate salt of methylecgonidine (MEG; anhydroecgonine methylester), a pyrolysis product of cocaine, has previously been shown to antagonize contractions of guinea pig isolated trachea induced by acetylcholine (ACh) and other spasmogenics. We determined the effects of MEG fumarate on ACh-induced bronchoconstriction in vivo. Specific airway conductance (SGaw) was measured in guinea pigs receiving 30-300 mg/kg s.c. MEG fumarate and exposed one hour later to nebulized ACh (0.2-3.2%; by inhalation). MEG fumarate did not induce any changes in SGaw; neither did it antagonize dose-dependent decreases in SGaw induced by ACh. However, tremors, salivation, startle and increased numbers of fecal boli were observed after MEG administration. Thus, unlike antagonism of ACh-induced contractions of guinea pig isolated trachea observed in vitro, MEG fumarate does not antagonize ACh-induced bronchoconstriction in vivo, even at doses which induced changes in grossly-observable behavior. Inhalation of a condensation aerosol of MEG base induced lung damage as evidenced by the presence of blood and higher levels of protein and lactate dehydrogenase in the lung lavage fluid of MEG-treated animals than of control animals. Aerosols of MEG fumarate, on the other hand, did not induce lung damage when inhaled. These results extend previous observations that MEG base may contribute to detrimental pulmonary effects of crack smoking.

Acetylcholine↗
PubMed1995

Purification of chlorpromazine-sensitive GTPase from rat cerebral cortex.

The chlorpromazine-sensitive GTPase from the cell membrane of rat cerebral cortex was purified to homogenity by using DEAE Bio-Gel A agarose, hydroxyapatite and heparin agarose chromatography. The purified chlorpromazine-sensitive GTPase was purified 370-fold to obtain a final specific activity of 40 mumol GTP hydrolyzed2min/mg protein. The purified enzyme was inhibited by chlorpromazine but not by compound 48/80. Magnesium was required for its activity instead of calcium. The purified enzyme had an apparent pH optimum of 8.0, and molecular weight was estimated to be 58,000.

Animals↗
PubMed1995

Effect of dietary retinyl palmitate on the promotion of altered hepatic foci by 3,3',4,4'-tetrachlorobiphenyl and 2,2',4,4',5,5'-hexachlorobiphenyl in rats initiated with diethylnitrosamine.

The purpose of this study was to determine the effects of dietary vitamin A on the tumor promoting effect of 3,3',4,4'-TCB and 2,2',4,4',5,5'-HCB in a two-stage rat hepatocarcinogenesis model with diethylnitrosamine (DEN, 150 mg/kg) as the initiator. Two weeks after DEN injection rats were fed a purified diet containing either 2000 or 100,000 IU of vitamin A in the form of retinyl palmitate. Rats received four biweekly injections of 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB (300 mumol/kg), or both (150 mumol/kg each) in corn oil (10 ml/kg) for 8 weeks. Control animals received vehicle only. Six rats in each group that received no DEN treatment were used as additional control animals. Ten days after the last injection the rats were killed. In rats fed the low retinyl palmitate diet, treatment with 3,3',4,4'-TCB, 2,2',4,4',5,5'-HCB or both compounds lowered hepatic retinyl palmitate content. This effect was prevented by high dietary retinyl palmitate supplementation in rats treated with 2,2',4,4',5,5'-HCB, but not 3,3',4,4'-TCB or both compounds together. Histopathological examination of the liver showed that high dietary retinyl palmitate lessened the severity of hepatocellular necrosis and fatty changes induced by 3,3',4,4'-TCB alone or in combination with 2,2',4,4',5,5'-HCB. The latter did not cause significant pathological lesions to the liver. However, high dietary retinyl palmitate was not able to prevent thymic involution caused by 3,3',4,4'-TCB. The number and volume of altered hepatic foci were increased by 2,2',4,4',5,5'-HCB and particularly 3,3',4,4'-TCB; no synergistic effect was seen. Supplementation with high dietary retinyl palmitate diminished the number and volume of foci. These results show that supplementation with high dietary retinyl palmitate protects against hepatocellular necrosis, fatty changes, and preneoplastic changes induced by 3,3',4,4'-TCB as well as against preneoplastic changes induced by 2,2',4,4',5,5'-HCB. In addition, these two agents did not synergistically induce preneoplastic changes in DEN-induced rats.

Animals↗
PubMed1995

Genetic relatedness of Cryptococcus neoformans clinical isolates grouped with the repetitive DNA probe CNRE-1.

Cryptococcus neoformans isolates from eight patients with cryptococcal infection were previously assigned into three groups on the basis of repetitive DNA probe (CNRE-1) restriction fragment length polymorphisms. These groups accounted for a disproportionate number of recent clinical isolates in New York City. To further examine the genetic relatedness of isolates within and across CNRE-1 groups, the DNA sequence of the 779-base URA5 gene from each strain was amplified and sequenced. The number of nucleotide differences occurred in the third codon position or in introns. Pairwise comparisons revealed average nucleotide differences within a CNRE-1 group of 4.8 +/- 2.6 (n = 8) and between CNRE-1 groups of 21.9 +/- 7.0 (n =20) (P <0.001) Analysis of URA5 sequences defined three groups that were congruent with those defined by CNRE-1 restriction fragment length polymorphisms. PCR amplification of an rDNA intergenic spacer revealed conservation of the intergenic spacer length within groups. Electrophoretic karyotyping did not distinguish between two isolates in each of two CNRE-1 groups. DNA from all isolates studied hybridized to an alpha mating type-specific probe. We interpret these results as suggesting a clonal population structure for some pathogenic isolates of C. neoformans in New York City.

Base Sequence↗
PubMed1995

Modulation of Ca2+ influx by a mediator released from human tracheal epithelial cells exposed to ozone in vitro.

Intracellular free Ca2+ ([Ca2+]i) plays a vital role both in maintaining normal cellular function and in cell killing. Few studies have been published regarding its role in ozone (O3)-induced health effects. This study investigated the effect and mechanism of O3 exposure on [Ca2+]i in human tracheal epithelial (HTE) cells. HTE cells grown on Costar Transwell inserts with a liquid-gas interface were exposed to 0, 0.05, 0.1, 0.2 and 0.4 ppm O3 at 37 degrees C for 1 h. After exposure, [Ca2+]i was measured using the fluorescent dye Fluo 3. O3 at 0.4 ppm produced a significant increase in [Ca2+]i, and the increases in [Ca2+]i were blocked by verapamil and 8-(diethylamino)-octyl-3,4,5,-trimethoxybenzoate (TMB-8). These results suggest that the O3-induced [Ca2+]i elevation may involve both Ca2+ release from internal stores and Ca2+ influx across the plasma membrane. Furthermore, both buffer and cell lysate of HTE cells exposed to 0.4 ppm O3 caused a rapid increase in [Ca2+]i of THP-1 human phagocytic monocytes, but the buffer and lysate from air exposed cells did not. These results suggest that O3 exposure causes HTE cells to release a diffusible mediator from the empty Ca(2+)-storing organelle and may be responsible for the sustained and persistent [Ca2+]i elevation in HTE cells exposed to 0.4 ppm O3.

Calcium↗
PubMed1994

Deletion of two separate regions on chromosome 3p in breast cancers.

We have characterized the copy number of various loci on chromosome 3p in a series of breast cancers. To determine the precise region(s) involved, restriction fragment length polymorphism (RFLP) analysis for loss of heterozygosity (LOH) was performed using a panel of RFLP probes at 3p13-14, 3p21-22, and 3p24-26. The incidence of LOH at the three loci was 41, 32, and 45%, respectively. To validate the LOH data and to gain insights into the mechanisms resulting in LOH, chromosome 3 pericentromeric and 3p region-specific DNA probes were used to determine the DNA copy number by fluorescence in situ hybridization (FISH). Among 22 cases examined, 15 showed loss by both LOH and FISH, indicating that the dominant mechanism of LOH at 3p in breast cancer is a physical deletion. Two of the 22 cases showed loss by RFLP analysis but not by FISH, suggesting either mitotic recombination or loss and endoreduplication. In three cases, RFLP analysis indicated allelic imbalance, which was incorrectly interpreted as LOH, since a gain of one allele was suggested by FISH. By constructing a deletion map, we found that 2 separate regions, 3p13-14 and 3p24-26, were independently deleted in some breast cancers. Additionally, four cases had break points within the 3p24-26 region and one case had a homozygous deletion at 3p13, further supporting the hypothesis that there are tumor suppressor genes at both 3p13-14 and 3p24-26. Although high frequency of LOH was observed at the 3p21-22 region, there was no direct evidence supporting the existence of a breast cancer tumor suppressor gene there as opposed to codeletion with either the proximal or distal region.

Blotting, Southern↗
PubMed1994

Effect of excess dietary retinoic acid on skin papilloma and carcinoma formation induced by a complete carcinogenesis protocol in female Sencar mice.

Previously, we have shown that dietary retinoic acid (RA) at pharmacological doses (30 micrograms/g of diet) inhibited the malignant conversion of skin papillomas to carcinomas induced by a two-stage carcinogenesis protocol with 7,12-dimethylbenz[a]anthracene as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter (De Luca et al., Carcinogenesis, 14 (1993) 539-542). The purpose of this study was to determine the effect of dietary RA on skin papilloma and carcinoma formation induced by a complete carcinogenesis protocol with repeated DMBA treatment in female Sencar mice. Mice at 3 weeks of age were weaned onto a diet containing either 3 (control) or 30 (excess) micrograms of RA/g of diet and treated topically with DMBA (25.5 micrograms) once per week for 20 weeks. Mice fed excess dietary RA did not significantly differ from control mice in the following parameters: body weight, survival rate, papilloma incidence, cumulative carcinoma incidence (19.4% versus 23.7%), carcinoma yield (0.19 versus 0.26 per mouse), carcinoma conversion efficiency (5.2% versus 3.9%), and average age of carcinoma development (22.7 +/- 4.7 versus 23.3 +/- 2.8 weeks). However, papilloma yield was decreased by about 50% (i.e. 3.7 versus 7.0 at week 20, P < 0.01) between weeks 17 and 22 of age by excess dietary RA treatment. Contrary to other routes of administration (i.e. topical and systemic) of RA (Verma et al., Cancer Res., 42 (1982) 3519-3525), excess dietary RA did not enhance skin tumor formation. In addition, excess dietary RA failed to inhibit malignant conversion of papillomas to carcinomas in the complete carcinogenesis protocol. Thus, the modulation of RA on skin papilloma and carcinoma formation is dependent on carcinogenesis protocol and route of RA administration.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Loss of heterozygosity and p53 gene mutations in breast cancer.

Immunopositivity for the p53 tumor suppressor gene product was evaluated in 133 breast cancers and compared to loss of heterozygosity (LOH) at various chromosomal loci. The validity of p53 immunopositivity as an indicator for p53 mutations was verified using two molecular assays of p53 mutations: single stranded conformational polymorphism (32 cases) and/or direct sequencing (14 cases). Immunopositivity was highly specific for mutations, since all of 15 strongly immunopositive tumors (> 10% of the cells are positive) and seven of nine cases with borderline immunopositivity had mutations by molecular analysis but were somewhat lower in sensitivity, p53 mutations being also detected in three of 23 (13%) immunonegative cases. LOH was measured at loci on the following chromosomes (1p,q; 2p; 3p; 7q; 11p,q; 13q; 16q; 17p; 18p,q; and 22q) by Southern blotting, polymerase chain reaction amplification of restriction fragment length polymorphisms, or repetitive cytidine and adenine stretches (CA repeats). There was no association between p53 mutations and one measure of genomic instability, namely, high incidence of overall LOH. In contrast, p53 mutations strongly associated with LOH at two specific loci, 3p24-26 (P < 0.001) and 7q31 (P < 0.05). There was no association between p53 mutations and LOH at 17p (site of the p53 gene), suggesting that breast cancers often have only one defective allele of the p53 gene.

Base Sequence↗
PubMed1994

Comparative biological potency of acidic sulfate aerosols: implications for the interpretation of laboratory and field studies.

Biological responses to inhaled acid sulfates result from the deposition of hydrogen ion (H+) on airway surfaces. Thus, effects from sulfuric acid and ammonium bisulfate, the two major ambient species, have been assumed to be the same for a given H+ concentration within the exposure atmosphere, assuming similar respiratory tract deposition patterns. However, recent inhalation studies have indicated that sulfuric acid is disproportionately potent compared to ammonium bisulfate when the H+ content of the exposure atmosphere is considered, suggesting that some factors following inhalation affect the amount of H+ contacting airway surfaces. This study assessed a mechanism potentially underlying this phenomenon, namely, the extent of neutralization by respiratory tract ammonia. This was evaluated using a physical model system designed to mimic transit of these aerosols in the upper respiratory tract of the animal model used in this laboratory, the rabbit. The results suggest that for equal exposure quantities of H+, more acid would be deposited when sulfuric acid is inhaled than when ammonium bisulfate is inhaled. Furthermore, results from a series of in vitro exposures of tracheal epithelial cells to sulfuric acid and ammonium bisulfate aerosols indicated that the biological response is a function of the total mass (ionic) concentration of H+ deliverable to the cells or the total extractable H+ per particle. The results of this study have possible implications for ambient monitoring of particulate-associated strong acidity, suggesting that it may be necessary to specilate such measures into the relative amounts of H+ as sulfuric acid or ammonium bisulfate in order to most accurately relate atmospheric acid levels to observed health effects. In addition, since much of the ambient particulate-associated H+ exists as sulfuric acid/ammonium bisulfate mixtures rather than pure compounds, H(+)-associated health effects from controlled exposure studies of sulfuric acid may not be transferable to ambient population situations on a 1:1 basis. Since any such errors in exposure assessment will necessarily bias downward the strength of H(+)-related health effects associations found via epidemiological studies, failure to address the specification of H+ may cause such studies to underestimate the human health effects of strong acids.

Aerosols↗
PubMed1994

Retinol and beta-carotene concentrations in skin, papillomas and carcinomas, liver, and serum of mice fed retinoic acid or beta-carotene to suppress skin tumor formation.

Using 7,12-dimethylbenz[a]anthracene as the initiator and 12-O-tetradecanoyl-13-acetate as the tumor promoter on the dorsal skin of Sencar mice, we previously showed that pharmacological dietary all-trans-retinoic acid and beta-carotene inhibit the conversion of papillomas to carcinomas in a two-stage system of chemical carcinogenesis. The purpose of this study was to determine the influence of dietary retinoic acid and beta-carotene on retinoid and beta-carotene concentrations in skin and other tissues. We were unable to measure tissue retinoic acid because of the relatively limited amount of tissue available for analysis and the fast rate of metabolism. Different dietary levels of retinoic acid or beta-carotene did not influence total retinol of skin, papilloma, and carcinoma tissues, which all showed a concentration of approximately 1 +/- 0.5 microgram/g wet wt. Equally refractory to dietary retinoic acid or beta-carotene was serum retinol concentration. In contrast, dietary retinoic acid protected loss of liver retinol and retinyl palmitate, and beta-carotene caused an increase in beta-carotene and retinyl palmitate in liver but did not affect serum and liver retinol. We further investigated metabolic and functional aspects of retinoic acid in cultured mouse epidermal keratinocytes (LC-8 cells) and found that these cells actively metabolized [10,11-14C]retinoic acid to polar compounds. Isomers of retinoic acid were a minor product in the presence of cells and the major product when incubated in serum-containing medium in the absence of cells. From the functional point of view, exposure of LC-8 cells to 3 x 10(-6) M all-trans-retinoic acid (RA) caused a 75-fold induction in tissue transglutaminase and an approximately 9-fold induction in 10(-6) M RA at three days of culture. We conclude that retinoic acid spares endogenous retinol and that beta-carotene greatly enhances liver retinyl palmitate levels. Moreover we show that although mouse epidermal cells metabolize retinoic acid at a very high rate, they respond functionally by induction of tissue transglutaminase activity. Because this enzyme has been suggested to be involved in programmed cell death, we are presently investigating the possibility that it may be involved in the inhibition of carcinogenesis in mice fed pharmacological doses of RA.

Animals↗
PubMed1994

High dietary retinoic acid prevents malignant conversion of skin papillomas induced by a two-stage carcinogenesis protocol in female SENCAR mice.

We have previously reported that high dietary retinoic acid (RA; 30 micrograms/g diet) inhibits carcinoma formation in a two-stage skin carcinogenesis protocol, using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as the tumor-promoter in female SENCAR mice. We next asked whether switching the diets from high to control levels of RA and vice versa would influence carcinoma formation. Mice at 3 weeks of age were initiated with DMBA (20 micrograms) once, followed by 20 weekly applications of TPA (2 micrograms). At 3 weeks of age mice were weaned onto a diet containing either 3 (control) or 30 (high) micrograms RA/g diet. Half of the mice from either dietary group were switched to the other diet at 20 weeks of age, when papilloma formation was at its peak. These four groups are designated RA 3 micrograms, RA 30 micrograms, RA 3/30 micrograms and RA 30/3 micrograms groups. As previously found, papilloma formation (including incidence and yield) was not significantly affected by dietary treatment. However, high dietary RA inhibited carcinoma formation; specifically cumulative carcinoma incidence (18.5-23.1% versus 50%) and yield (0.19-0.23 versus 0.68) were significantly lower (P < 0.05) in the high dietary RA treatment groups than the RA 3 micrograms control group, as was the carcinoma conversion efficiency (2.1-3.8% versus 9.4%). The beneficial effect on carcinoma formation was still evident when excess RA was given late during the carcinogenesis process (i.e. the RA 3/30 micrograms group). Moreover, a residual effect of excess RA was also seen after the dietary RA was switched to the control level at 20 weeks of age, when papilloma yield was highest (i.e. the RA 30/3 micrograms group). It is therefore concluded that the chemopreventive effect of high dietary RA on skin carcinogenesis induced by a two-stage carcinogenesis protocol with DMBA and TPA resides mainly at the step of conversion from benign papillomas to malignant carcinomas.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1994

Inhalation of steady-state sidestream smoke from one cigarette promotes arteriosclerotic plaque development.

BACKGROUND: A number of epidemiologic studies have suggested that every year environmental tobacco smoke (second-hand smoke) is responsible for tens of thousands of deaths, mostly from heart disease, in the United States. Environmental tobacco smoke is composed mainly (80% to 85%) of aged and diluted sidestream smoke. The remainder is exhaled mainstream smoke. Among the thousands of compounds that have been identified in environmental tobacco smoke are a number of carcinogens, including polynuclear aromatic hydrocarbon carcinogens, such as benzo(a)pyrene. We have demonstrated previously that a number of carcinogens, including benzo(a)pyrene, promote plaque development after injection into cockerels. There have been almost no studies showing a direct stimulatory effect of environmental tobacco smoke on plaque development. Recently we demonstrated that cockerels exposed to sidestream smoke for approximately 0.4% of their projected lifespan exhibited accelerated development of arteriosclerotic plaques. In that study, cockerels in specially designed inhalation chambers were exposed to the steady-state sidestream smoke from 5 cigarettes for 6 h/d for 16 weeks. This level of exposure is high but environmentally plausible. Statistically significant increases in plaque size were demonstrated in the smoke-exposed cockerels. METHODS AND RESULTS: In the present study, exposure levels were decreased by a factor of 5. Thirty cockerels were exposed to the steady-state sidestream smoke from 1 cigarette for 6 hours per day for 16 weeks. The smoke was mixed with filtered air. Ten control cockerels were exposed to filtered air only. Levels of smoke surrogates, including carbon monoxide and total suspended particulates, were measured three times a day. Again, there was a statistically significant increase in plaque size in the smoke-exposed cockerels. To place these studies within a context of environmental relevance, levels of carbon monoxide were measured independently over 1 to 3 hours in four bars where there was heavy smoking. Measured carbon monoxide levels were as high or higher in the bars than they were in the exposure chambers during the 1-cigarette sidestream-smoke study. CONCLUSIONS: Experimental exposure to secondhand smoke at levels equal to or even below those routinely encountered by people in smoke-filled environments is sufficient to promote arteriosclerotic plaque development.

Animals↗
PubMed1993

Disruption of the cysteine-75 and zinc ion coordination is not sufficient to activate the precursor of human matrix metalloproteinase 3 (stromelysin 1).

Matrix metalloproteinases (MMPs) are activated in vitro from their precursors (proMMPs) by multiple means such as treatment with proteinases, mercurial compounds, chaotropic agents, sodium dodecyl sulfate, HOCl, and heat. The latency of proMMPs is stabilized by intramolecular interaction of the single cysteine residue in the conserved sequence PRCG(V/N)PD of the propeptide and the zinc atom at the active site. The activation of proMMP-1 (interstitial procollagenase) by multiple treatments has been explained by the "cysteine switch" model, in which the disruption of the Cys-Zn interaction is considered to be critical for activation [Springman, E. B., Angleton, E. L., Birkedal-Hansen, H., & VanWart, H. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 364-368]. To further test this hypothesis we dissociated the Cys-Zn interaction by specifically modifying Cys-75 of proMMP-3 (prostromelysin 1) with iodoacetamide, (4-aminophenyl)mercuric acetate (APMA), or 5,5'-dithiobis(2-nitrobenzoate) and examined the expression of enzymic activity. The enzymic assays of the modified proMMP-3s against protein and synthetic substrates did not reveal any significant activity. The modified 57-kDa proMMP-3s were stable and did not show spontaneous activation. Activation of the modified proMMP-3s required further treatment with APMA or a proteinase and was accompanied by conversion of the proMMP-3 to a 45-kDa species. Circular dichroism studies of proMMP-3 treated with HgCl2 demonstrated time-dependent conformational changes in proMMP-3 prior to the expression of proteolytic activity and processing of the zymogen to lower molecular weight species. These results indicate that the disruption of the Cys-Zn coordination alone is not sufficient to activate proMMP-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗
PubMed1993

A novel system for the in vitro exposure of pulmonary cells to acid sulfate aerosols.

While ambient acid aerosols are considered a potential respiratory health hazard, the mechanism by which they induce responses in the lungs is not known. Attempts to ascertain these mechanisms using inhalation exposures are complicated by a number of technical difficulties, chief among which are neutralization of inhaled acids by endogenous ammonia and variations in deposition with inhaled particle size. To control for these variables, a novel in vitro exposure system allowing experimental evaluation of factors which influence biologic responses to acid sulfate particles was developed. The system consists of two subunits, a generation/delivery component and a cell exposure component. Sulfuric acid aerosols are generated by nebulizing dilute acid solutions. Particles larger than a specified size of interest (based upon the specific exposure conditions desired) are removed, and particles at the desired size and mass concentration are uniformly delivered onto a target cell monolayer. The system is capable of delivering acid particles larger than 0.7 micron (mass median diameter), yet at constant particle mass concentrations. This paper describes the design of the exposure system and its performance characteristics and presents initial results of some biological responses obtained using it. In conjunction with inhalation studies, this exposure system may provide additional insights into mechanisms by which acid aerosols adversely affect the respiratory tract and into the physical characteristics of acid particles which modulate toxicity.

Aerosols↗