Biomedical subjects

Terry Gordon

Publications and source records attributed to Terry Gordon.

At least 19 recordsLinked to original sources

PubMed2006

The parity-related protection against breast cancer is compromised by cigarette smoke during rat pregnancy: observations on tumorigenesis and immunological defenses of the neonate.

Early pregnancy is a powerful negative risk factor for breast cancer (BCa) in women. Pregnancy also protects rats against induction of BCa by carcinogens such as N-methyl-N-nitrosourea (MNU), making the parous rat a useful model for studying this phenomenon. Smoking during early pregnancy may lead to an increased risk of BCa in later life, possibly attributable to carcinogens in cigarette smoke (CS), or to reversal of the parity-related protection against BCa. To investigate these possibilities, 50-day-old timed first-pregnancy rats were exposed to standardized mainstream CS (particle concentration = 50 mg/m3) or to filtered air (FA) 4 h/day, Day 2-20 of gestation. Age-matched virgin rats were similarly exposed to CS or FA. At age 100 days, the CS or FA-exposed, parous and virgin rats were injected s.c. with MNU (50 mg/kg body wt), or with MNU vehicle. Mammary tumors (MTs) first appeared in virgin rats 9 weeks post-MNU injection. While no MTs were detected in FA-exposed parous rats until 18 weeks post-MNU, MTs appeared in the CS-exposed parous rats as early as 10 wks (P < 0.02). As no MTs developed in CS-exposed rats not injected with MNU, CS did not act as a direct mammary carcinogen. Serum prolactin concentration on Day 19 of pregnancy in CS-exposed dams was reduced by 50% compared with FA-exposed dams (P < 0.005). CS exposure during a pregnancy may thus 'deprotect' rats, enhancing their vulnerability to MNU-induced BCa. Prenatal CS exposure had no detectable effect on the immune responses of the pups examined at 3, 8 or 19 weeks of age. However, prolactin concentration in stomach contents (milk) of 3-day-old pups suckled by CS-exposed dams was decreased when compared with that of FA-exposed dams (P < 0.032). As milk-borne prolactin modulates development of the central nervous and immune systems of neonatal rats, CS exposure of the dams could adversely affect later maturation of these systems by reducing milk prolactin.

Animals↗

PubMed2006

History and results of the two inter-laboratory round robin endotoxin assay studies on cotton dust.

BACKGROUND: In the US cotton industry, airborne cotton dust levels are regulated, and other countries are moving to specify safety limits for airborne endotoxins. There is concern about potential respiratory health hazards associated with agricultural and other organic dusts. In laboratories, ranking which samples have high and low levels of endotoxin is usually in good agreement between laboratories. When different laboratories assay identical samples, the levels differ. The objective of this research was to evaluate the intra- and inter-laboratory variability for 13 laboratories measuring endotoxin in cotton dust. METHOD: Two inter-laboratory round robin endotoxin assay studies were conducted using cotton dust. In the first round robin, each laboratory used their normal in-house assay method and then used a common extraction protocol. In the second round robin, a common extraction protocol and endotoxin assay kit was used. RESULTS: The intra-laboratory results had small variations but inter-laboratory results had very high variations. The inter-laboratory results using a common extraction protocol showed reduced differences. Using the same extraction protocol and endotoxin assay kit, the intra-laboratory variation was small and inter-laboratory variation was reduced but not enough for inter-laboratory agreement. Most of the laboratories were able to discern between the high and low endotoxin concentration dusts. CONCLUSIONS: Standardization has reduced the differences in results between laboratories and possibly further standardization may bring closer inter-laboratory agreement.

Air Microbiology↗

PubMed2006

Mycobacterium immunogenum causes hypersensitivity pneumonitis-like pathology in mice.

A surprising number of cases of hypersensitivity pneumonitis have been observed at work sites employing automotive machinists. Because hypersensitivity pneumonitis is not typically associated with exposure to metalworking fluid aerosols, this study examined whether Mycobacterium immunogenum (M. immunogenum), a rapidly growing mycobacterium isolated from several affected work sites, could induce hypersensitivity pneumonitis in mice. Hypersensitivity pneumonitis-like histologic changes occurred in mice treated with heat-killed and lysed M. immunogenum. These lung lesions were characterized by peribronchial and perivascular lymphohistiocytic inflammation and noncaseating granulomas in the parenchyma. The pathologic changes observed in mice instilled with M. immunogenum-contaminated used metalworking fluid were indistinguishable from those observed with M. immunogenum alone. The role of genetic factors in M. immunogenum-induced lung lesions was examined by comparison of the response of eight inbred strains of mice. The observed immunologic changes in the lung were significantly greater in C57Bl/6, 129, and BALB/c mice than in the other strains, suggesting that genetic factor(s) contribute to the susceptibility of workers exposed to M. immunogenum-contaminated metalworking fluid aerosols. Thus, these studies provide indirect evidence that M. immunogenum is an unrecognized class of microorganisms capable of causing hypersensitivity pneumonitis and plays a role in the outbreaks of hypersensitivity pneumonitis in automotive plants.

Aerosols↗

PubMed2005

International Workshop on the Design and Analysis of Experimental Studies using PM Concentrator Technologies, Boston, May 5, 2004.

A workshop that brought together representatives of most of the laboratories that have conducted animal and/or human inhalation exposure studies with concentrated ambient air particles (CAPs) was convened by the Health Effects Institute in Boston on May 5, 2004. Participants agreed that CAPs researchers need to make serious efforts to harmonize their experimental and analytical protocols to permit the sharing of lessons learned, questions raised, and opportunities for more definitive studies. Standardized outcome measures based on spirometry and response markers in lung bronchoalveolar lavage (BAL) cells and fluids exist, including the appropriate times after exposure to collect samples and measurements. However, for the emerging focus on cardiac system responses, there are many different electrocardiographic (ECG) endpoints being examined, and little standardization on markers that are most informative about adverse effects; on when the measurements need to be made; and on how to make comparable measurements. The workshop focused on two aspects of dealing with these complexities: sorting out influential particulate matter (PM) components responsible for observed effects, and searching for time-varying responses in continuous outcome data. The need for more complete analyses of PM samples from the CAPs studies was also emphasized, as was obtaining a consistent set of parameters characterizing exposure atmospheres and the ambient PM from which the CAPs are sampled. CAPs studies have already had a significant impact within the air pollution health effects community, especially in regard to cardiovascular system effects, and a follow-up meeting with a greater focus on means to harmonize data collection and analysis is needed.

Air Pollutants↗

PubMed2005

Quantitative trait analysis of the development of pulmonary tolerance to inhaled zinc oxide in mice.

BACKGROUND: Individuals may develop tolerance to the induction of adverse pulmonary effects following repeated exposures to inhaled toxicants. Previously, we demonstrated that genetic background plays an important role in the development of pulmonary tolerance to inhaled zinc oxide (ZnO) in inbred mouse strains, as assessed by polymorphonuclear leukocytes (PMNs), macrophages, and total protein in bronchoalveolar lavage (BAL) phenotypes. The BALB/cByJ (CBy) and DBA/2J (D2) strains were identified as tolerant and non-tolerant, respectively. The present study was designed to identify candidate genes that control the development of pulmonary tolerance to inhaled ZnO. METHODS: Genome-wide linkage analyses were performed on a CByD2F2 mouse cohort phenotyped for BAL protein, PMNs, and macrophages following 5 consecutive days of exposure to 1.0 mg/m3 inhaled ZnO for 3 hours/day. A haplotype analysis was carried out to determine the contribution of each quantitative trait locus (QTL) and QTL combination to the overall BAL protein phenotype. Candidate genes were identified within each QTL interval using the positional candidate gene approach. RESULTS: A significant quantitative trait locus (QTL) on chromosome 1, as well as suggestive QTLs on chromosomes 4 and 5, for the BAL protein phenotype, was established. Suggestive QTLs for the BAL PMN and macrophage phenotypes were also identified on chromosomes 1 and 5, respectively. Analysis of specific haplotypes supports the combined effect of three QTLs in the overall protein phenotype. Toll-like receptor 5 (Tlr5) was identified as an interesting candidate gene within the significant QTL for BAL protein on chromosome 1. Wild-derived Tlr5-mutant MOLF/Ei mice were tolerant to BAL protein following repeated ZnO exposure. CONCLUSION: Genetic background is an important influence in the acquisition of pulmonary tolerance to BAL protein, PMNs, and macrophages following ZnO exposure. Promising candidate genes exist within the identified QTL intervals that would be good targets for additional studies, including Tlr5. The implications of tolerance to health risks in humans are numerous, and this study furthers the understanding of gene-environment interactions that are likely to be important factors from person-to-person in regulating the development of pulmonary tolerance to inhaled toxicants.

Air Pollutants↗

PubMed2005

Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice. I. Introduction, objectives, and experimental plan.

This subchronic (6-mo) inhalation study of the effects of concentrated ambient air fine particulate matter (PM2.5) in normal mice (C57) and a murine model of humans with an advanced level of aortic plaque (ApoE-/- or ApoE-/- LDLr-/-) was designed to determine the presence and extent of a variety of health-related responses. The animals were exposed for 6 h/day, 5 day/wk during the spring and summer of 2003 to concentrations that were elevated 10-fold in Tuxedo, NY, a regional background site that is upwind and approximately 50 km west-northwest of New York City. The average PM2.5 concentration during exposure was 110 microgram/m3, and the long-term average was 19.7 microg/m3. There were substantial daily variations in concentration, and we sought evidence both for the influence of peak exposures on acute responses and for the cumulative effects of the prolonged series of exposures. Acute responses were characterized in terms of: (1) short-term electrocardiographic (EKG), core body temperature, and physical activity differences between PM and sham-exposed mice; and (2) in vitro toxicity of a simultaneously collected PM2.5 sample to lung epithelial cells. Cumulative responses to PM2.5 were characterized in terms of changes in heart rate, heart-rate variability, heart-rate variance, aortic plaque density, genetic marker expression, and brain cell distributions. There were no significant changes in the normal mice. The nature and extent of the exposure-related responses that were seen in the ApoE-/- as well as ApoE-/- LDLr-/- mice are described in the articles that follow in this special issue of Inhalation Toxicology.

Aerosols↗

PubMed2005

Effects of subchronic exposures to concentrated ambient particles in mice. IX. Integral assessment and human health implications of subchronic exposures of mice to CAPs.

In order to examine the biologic plausibility of adverse chronic cardiopulmonary effects in humans associated with ambient particulate matter (PM) exposure, we exposed groups of normal mice (C57) and knockout mice that develop atherosclerotic plaque (ApoE-/- and ApoE-/- LDLr-/-) for 6 h/day, 5 days/wk for 5 or 6 mo during the spring/summer of 2003 to either filtered air or 10-fold concentrated ambient particles (CAPs) in Tuxedo, NY (average PM2.5 concentration during exposure = 110 microg/m3). Some of the mice had implanted electrocardiographic monitors. We demonstrated that: (1) this complex interdisciplinary study was technically feasible in terms of daily exposure, collection of air quality monitoring data, the collection, analysis, and interpretation of continuous data on cardiac function, and the collection and analyses of tissues of the animals sacrificed at the end of the study; (2) the daily variations in CAPs were significantly associated, in ApoE-/- mice, with daily variations in cardiac functions; (3) there were significant differences between CAPs and sham-exposed ApoE-/- mice in terms of cardiac function after the end of exposure period, as well as small differences in atherosclerotic plaque density, coronary artery disease, and cell density in the substantia nigra in the brain in the ApoE-/- mice; (4) there are suggestive indications of gene expression changes for genes associated with the control of circadian rhythm in the ApoE-/- LDLr-/- double knockout (DK) mice. These various CAPs-related effects on cardiac function and the development of histological evidence of increased risk of clinically significant disease at the end of exposures in animal models of atherosclerosis provide biological plausibility for the premature mortality associated with PM2.5 exposure in human subjects and provide suggestive evidence for neurogenic disease as well.

Air Pollutants↗

PubMed2004

Six month tracking of microbial growth in a metalworking fluid after system cleaning and recharging.

Large volumes of metalworking fluids (MWFs) are used in manufacturing industries for cooling and lubrication of metal pieces and tools during machining. MWFs accumulate microbial growth through continuous recirculation and reuse. We studied the progression of microbial contamination for 6 months after dumping, cleaning and recharging (DCR) of a large semi-synthetic MWF system managed with several biocides. Fresh, uncontaminated fluid was added to the system after extensive cleaning. The following samples were collected and analyzed: pre-DCR fluid (before system cleaning); neat fluid diluted to 6% with water; in use MWF 12 h and 1, 3 and 6 months post-DCR. Samples were analyzed for total microorganism concentrations by direct counting using fluorescence microscopy and by plate counting on various media (R2A, BHI, Middlebrooks and rose bengal under aerobic conditions). In addition, PCR was performed for the detection of mycobacteria. There was a rapid progression in the total bacterial counts as determined by fluorescence microscopy: 5.7 x 10(7) cells/ml in the pre-DCR used fluid, no measurable bacteria in the neat fluid, 6.9 x 10(6) cells/ml after 12 h and 2.2 x 10(6), 3.6 x 10(8) and 6.1 x 10(8) cells/ml after 1, 3 and 6 months, respectively. On average, only 0.2% of the direct count organisms were quantified on R2A cultures. PCR showed the presence of mycobacteria in the used MWF at 3 and 6 months. Mycobacteria were also identified from cultures on Middlebrooks and R2A. This study demonstrates that standard methods for cleaning MWF systems are inadequate since residual bacteria in the system can rapidly repopulate the newly charged MWF.

DNA, Bacterial↗

PubMed2004

Metalworking fluid--the toxicity of a complex mixture.

Various chemicals are used in the manufacture of cooling and lubricating fluids and fall into the classes of straight, soluble, semisynthetic, and synthetic metalworking fluids. The diversity of chemicals and in-use contaminants makes the risk assessment of metalworking fluids quite difficult. Toxicologists have used a number of methods to evaluate the component(s) responsible for the adverse pulmonary effects of metal working fluid aerosols encountered in the workplace. Although investigators have studied the adverse effects of metalworking fluid chemicals alone and in combination, the majority of evidence strongly suggests that the microbial changes that occur in fluid composition, during use and storage in the workplace, are responsible for the pulmonary effects reported for workers exposed to metalworking fluid aerosols. This review discusses the methodologies used to examine the toxicity of the complex nature of modern metalworking fluids and the findings that point toward bacterial endotoxin as a major contributor to their adverse effects.

Aerosols↗

PubMed2004

The Collaborative Cross, a community resource for the genetic analysis of complex traits.

The goal of the Complex Trait Consortium is to promote the development of resources that can be used to understand, treat and ultimately prevent pervasive human diseases. Existing and proposed mouse resources that are optimized to study the actions of isolated genetic loci on a fixed background are less effective for studying intact polygenic networks and interactions among genes, environments, pathogens and other factors. The Collaborative Cross will provide a common reference panel specifically designed for the integrative analysis of complex systems and will change the way we approach human health and disease.

Animals↗

PubMed2004

Effect of particulate and gaseous pollutants on spontaneous arrhythmias in aged rats.

Epidemiology studies suggest that exposure to air pollution increases the frequency of cardiac arrhythmias. A limitation of these studies is that it is difficult to link an increased risk of arrhythmias to a specific air pollutant. Animal exposure studies offer the opportunity to examine the effects of concentrated ambient fine particulate matter (PM), ultrafine PM, and copollutant gases separately. Male Fischer 344 rats, aged 18 mo, with implanted electrocardiograph (ECG) transmitters were used to determine the effects of PM on the frequency of arrhythmias. We found that old F344 rats had many spontaneous arrhythmias. An arrhythmia classification system was developed to quantify arrhythmia frequency. Arrhythmias were broadly grouped into two categories: premature beats and delayed beats. The rats were exposed to concentrated ambient PM (CAPS) or air for 4 h. The rats were exposed twice with a crossover design so each rat could serve as its own control. The CAPS concentrations were 160 microg/m(3) and 200 microg/m(3) for the first and second exposures, respectively. There was a significant increase in the frequency of irregular and delayed beats after exposure to CAPS. The same rats were subsequently exposed to laboratory-generated ultrafine carbon particles, to SO(2), or to air with a repeated crossover design. In these experiments there was no significant change in the frequency of any category of spontaneous arrhythmia following exposure to ultrafine carbon or SO(2). Thus, this study adds supporting evidence that acute exposure to elevated levels of ambient PM increases the frequency of cardiac arrhythmias.

Aging↗

PubMed2003

Beryllium: genotoxicity and carcinogenicity.

Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

Air Pollutants, Occupational↗

PubMed2003

Adaptation to stress induced by restraining rats and mice in nose-only inhalation holders.

There are limited data on the efficacy of procedures for adapting rodents to restraint in nose-only holders. We examined: (1) What effect does restraint in nose-only holders have on heart rate and body temperature? (2) Does a gradual increase in the duration of restraint facilitate adaptation? (3) How long does it take for rodents to become fully adapted to nose-only holders? (4) Do rats and mice respond and adapt similarly to restraint in nose only holders? Heart rate and body temperature were monitored as measures of stress using electrocardiograph (ECG) transmitters in male C57Bl/6J mice and Sprague-Dawley rats. In naive animals during the first hour of restraint, heart rate increased by 58 beats per minute (BPM) (18.6%) in rats and by 174 BPM (32.3%) in mice as compared to cage controls. Temperature increased by 2 degrees C in mice and was unchanged in rats compared to cage controls. Heart rate and temperature values remained within normal physiologic values during restraint. In rats, the response to restraint in nose-only holders was the same after 4 days regardless of whether the duration of restraint was increased gradually to 4 h/day or kept constant at 4 h/day. In mice, the group that was gradually adapted had a statistically significant higher heart rate and temperature after 4 days than the fixed-duration adapted group. Rats and mice restrained for 4 h/day every day showed a gradual decrease in heart rate and temperature over time. Full adaptation to restraint required 14 days of fixed-duration daily restraint.

Adaptation, Psychological↗

PubMed2003

Effects of inhaled ambient particulate matter on pulmonary antimicrobial immune defense.

Respiratory-tract infection, specifically pneumonia, contributes substantially to the increased morbidity and mortality among elderly individuals exposed to airborne particulate matter of <10 microm diameter (PM(10)). These epidemiological findings suggest that PM(10) may act as an immunosuppressive factor that can undermine normal pulmonary antimicrobial defense mechanisms. To investigate whether, and how, compromised pulmonary immunocompetence might contribute to increased mortality, two sets of laboratory studies were performed. The first examined the effects of a single inhalation exposure to concentrated ambient PM(2.5) (CAPS) from New York City air on pulmonary/systemic immunity and on the susceptibility of exposed aged rats to subsequent infection with Streptococcus pneumoniae. The second set of studies determined whether CAPS exposure, at a concentration approximating or somewhat greater than the promulgated 24-h NAAQS of 65 microg/m(3), could exacerbate an ongoing infection. Taken together, results demonstrated that a single exposure of healthy animals to CAPS had little effect on pulmonary immune function or bacterial clearance during subsequent challenge with S. pneumoniae. Alternatively, CAPS exposure of previously infected rats significantly increased bacterial burdens and decreased percentages of lavageable neutrophils and proinflammatory cytokine levels compared to those in infected filtered-air-exposed controls. These studies demonstrate that a single exposure to ambient PM(2.5) compromises a host's ability to handle ongoing pneumococcal infections and support the epidemiological findings of increased pneumonia-related deaths in ambient PM-exposed elderly individuals.

Aging↗

PubMed2003

Airway epithelial cells release MIP-3alpha/CCL20 in response to cytokines and ambient particulate matter.

The initiation and maintenance of airway immune responses in Th2 type allergic diseases such as asthma are dependent on the specific activation of local airway dendritic cells (DCs). The cytokine microenvironment, produced by local cells, influences the recruitment of specific subsets of immature DCs and their subsequent maturation. In the airway, DCs reside in close proximity to airway epithelial cells (AECs). We examined the ability of primary culture human bronchial epithelial cells (HBECs) to synthesize and secrete the recently described CC-chemokine, MIP-3alpha/CCL20. MIP-3alpha/CCL20 is the unique chemokine ligand for CCR6, a receptor with a restricted distribution. MIP-3alpha/CCL20 induces selective migration of DCs because CCR6 is expressed on some immature DCs but not on CD14+ DC precursors or mature DCs. HBECs were stimulated with pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin (IL)-1beta or, because of their critical role in allergic diseases, IL-4 and IL-13. Cells were also exposed to small size-fractions of ambient particulate matter. Each of these stimuli induced MIP-3alpha/CCL20 gene and protein expression. Moreover, these agents upregulated mitogen-activated protein kinase pathways in HBECs. Inhibition of the ERK1/2 pathway or p38 reduced cytokine-induced MIP-3alpha/CCL20 expression. These data suggest a mechanism by which AEC may facilitate recruitment of DC subsets to the airway.

Air Pollutants↗

PubMed2002

Crucial role of interleukin-1beta and nitric oxide synthase in silica-induced inflammation and apoptosis in mice.

Crystalline silica stimulates macrophages in vitro to release interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and nitric oxide (NO) and induces apoptosis of macrophages. Because the fibrogenic potential of a particulate paralleled its ability to induce apoptosis in macrophages, we investigated the underlying mechanisms by which IL-1beta and NO mediate apoptosis and inflammation in murine silicosis. First, we demonstrated that silica induced NO production and apoptosis in vitro using the IC-21 macrophage cell line. Both NO release and apoptosis could be inhibited by neutralizing anti-IL-1beta antibody or the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine-methyl ester (L-NAME), demonstrating the requirement for IL-1beta-mediated NO release in silica-induced apoptosis. We exposed IL-1beta knockout (IL-1beta(-/-)) mice, inducible NOS knockout (iNOS(-/-)) mice, and wild-type mice to 250 mg/m(3) silica for 5 h/d for 10 d using an inhalation chamber. Exposure of wild-type mice to silica resulted in lung inflammation, apoptosis, and significantly larger and more numerous silicotic lesions than in IL-1beta(-/-) mice over a 12-wk course. We also exposed iNOS(-/-) mice via inhalation in the same protocol and compared with wild-type mice and demonstrated that iNOS(-/-) mice had significantly reduced apoptosis and inflammation. These results demonstrated an association between apoptosis and inflammation in murine silicosis and support a potential role for IL-1beta-dependent NO-mediated apoptosis in the evolution of silicosis.

Analysis of Variance↗

PubMed2002

Ozone differentially modulates airway responsiveness in atopic versus nonatopic guinea pigs.

While acute exposures to ozone (O(3)) can alter airway responsiveness, effects from long-term exposures at low concentrations are less clear. This study assessed whether such exposures could induce nonspecific hyperresponsiveness in nonatopic (nonsensitized) guinea pigs and/or could exacerbate the pre-existing hyperresponsive state in atopic (sensitized) animals, and whether gender was a factor modulating any effect of O(3). Responsiveness was measured during and following exposures to 0.1 and 0.3 ppm O(3) for 4 h/day, 4 days/wk for 24 wk in male and female nonsensitized animals, those sensitized to allergen (ovalbumin) prior to initiation of O(3) exposures, and those sensitized concurrently with exposures. Ozone did not produce hyperresponsiveness in nonsensitized animals, but did exacerbate hyperresponsiveness to both specific and nonspecific bronchoprovocation challenges in sensitized animals, an effect that persisted through at least 4 wk after exposures ended. Gender was not a factor modulating response to O(3). Induced effects on responsiveness were not associated with numbers of eosinophils in the lungs nor with any chronic pulmonary inflammatory response, but were correlated with antigen-specific antibodies in blood. This study supports a role for chronic O(3) exposure in the exacerbation of airways dysfunction in a certain segment of the general population, namely, those demonstrating atopy.

Airway Resistance↗

PubMed2002

In vitro bioavailability of heavy metals in pressure-treated wood dust.

Pressure treatment with chromium, copper, and arsenic (CCA) is the most prevalent method for protecting wood used in outdoor construction projects. Although these metals are tightly bound to the wood fibers and are not released under most conditions of use, we examined the bioavailability of metals in CCA pressure-treated wood dust in vitro. Cytotoxicity and metallothionein (MT) mRNA expression were examined in V79 Chinese hamster lung fibroblast cells incubated with respirable-size wood dust generated by sanding CCA-treated and untreated (control) Southern yellow pine. In colony survival studies, increased cytotoxicity (p < 0.05) occurred in V79 cells treated with CCA wood dust (351 +/- 77 microg/ml, mean +/- SE) compared with control wood dust (883 +/- 91 microg/ml). Increased cytotoxicity with CCA wood dust also occurred in an arsenic resistant subline of V79 cells, thus suggesting that arsenic was not responsible for the increased cytotoxicity. Metallothionein mRNA was significantly increased after 48 h of treatment with CCA wood dust compared with control wood dust. Incubation of CCA wood dust in cell culture media resulted in the transfer of copper, but not chromium or arsenic, into the media. Moreover, the treatment of cells with this filtered extract resulted in significantly increased metallothionein mRNA, suggesting that bioavailable copper is responsible for inducing metallothionein mRNA in V79 cells. Thus, these bioassays suggest that metals become bioavailable during in vitro culture of phagocytic V79 cells with CCA wood dust.

Animals↗