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PubMedDate not supplied

Relationships between nitrogen dioxide personal exposure and ambient air monitoring measurements among children in three French metropolitan areas: VESTA study.

In epidemiological studies, investigators have routinely used ambient air concentrations, measured by air-quality monitoring networks, to assess exposure of subjects. When there is great spatial variability of ambient air concentrations or when there are specific indoor exposures, this approach may yield substantial exposure misclassification and distort the associations between exposure and the health endpoints of interest. In 3 French metropolitan areas, the cross-sectional relationships between 48 hr of nitrogen dioxide personal exposure of 73 children and the corresponding 48-hr background ambient air concentrations were analyzed. The crude correlation between ambient air concentrations and personal exposures was poor in all cities (r2 = .009 for Grenoble, r2 = .04 for Toulouse, and r2 = .02 for Paris). These correlations were improved when the authors took into account other ambient air or indoor air sources of nitrogen dioxide emissions (the corresponding multiple linear regression, r2, increased to .43 in Grenoble, .50 in Toulouse, and .37 in Paris). The main variables that explained personal exposures were an index of traffic intensity and proximity and use of a gas cooker at home. The results of this study confirm that ambient air-monitoring site measurements are poor predictors of personal exposure. Investigators should carefully characterize the proximity of roads occupied by dense traffic to the home/school as well as indoor sources of nitric oxide emissions; both of these careful characterizations will assist researchers in the prediction of personal exposure in epidemiological studies.

Adolescent↗

PubMed1996

In vivo exposure to nitrogen dioxide (NO2) induces a decrease in calcitonin gene-related peptide (CGRP) and tachykinin immunoreactivity in guinea-pig peripheral airways.

The mammalian respiratory tract is densely innervated by sensory and autonomic fibres. Subsets of the nerves contain bioactive regulatory peptides, such as substance P, calcitonin gene-related peptide (CGRP), and neurokinins. The sensory nervous system responds to inhaled irritants, resulting in a release of neuropeptides and, thus, a decrease in the peptide immunoreactivity of the fibres. We examined the effects of inhaled nitrogen dioxide (NO2), a well-known indoor and outdoor air pollutant, on pulmonary sensory neuropeptides. Guinea-pigs were exposed for 4 h to 18 parts per million (ppm) NO2 or to air (n = 5 each). At the end of the exposure, they were killed with urethane and their lungs were fixed in 1% paraformaldehyde in phosphate-buffered saline. Cryostat sections were stained with antisera to an anatomical nerve marker, protein gene product (PGP) 9.5, and to CGRP and tachykinins, utilizing the avidin-biotinylated peroxidase method. In the noncartilaginous airways (diameter < 250 microns) of NO2-exposed animals, less tachykinin- and CGRP-immunoreactive nerve fibres were found compared with controls. No change was seen in the total nerve fibre distribution (PGP 9.5). It is concluded that the peptidergic nerves of guinea-pig peripheral airways are a sensitive indicator of exposure to nitrogen dioxide.

Administration, Inhalation↗

PubMed1987

Effects of inhaled nitrogen dioxide and diesel exhaust on developing lung.

This study examined age-related differences in the physiological responses of rats to inhaled automotive emissions. Previous reports suggested that lung development of animals exposed to oxidant gases early in life might be impaired, or that developing lungs might be more susceptible than adult lungs to inhaled toxicants. There were no previous comparisons in developing and adult lungs of the effects of atmospheres containing particles. The hypothesis tested in this study was that rats exposed to chronically inhaled nitrogen dioxide (NO2) or diesel exhaust during lung development were more susceptible to lung injury than rats that were exposed to these atmospheres as adults. Rats were exposed either throughout the period of lung development or as adults, and health effects in the two groups were compared at the end of exposure. Rats were exposed seven hours per day, five days per week for six months to NO2 at 9.5 ppm, to whole diesel exhaust diluted to a soot concentration of 3.5 mg/m3, or to filtered air as controls. These concentrations were selected to produce mild effects in adults. The younger group (developing) was conceived in the exposure atmospheres and exposed during gestation and through the age of six months, and the older group (adult) was exposed between six and twelve months of age. Health effects were evaluated at the end of six months' exposure and some measurements were repeated six months after the cessation of exposure. Measurements included respiratory function, pulmonary immune responses, lung clearance of radiolabeled particles, airway fluid enzymes, protein and cytology, lung tissue collagen and proteinases, lung burdens of diesel soot, lung morphometry and histopathology. Nitrogen dioxide slightly reduced body weight and altered airway fluid enzymes of both age groups, with a greater number of statistically significant differences detectable in the enzyme levels of animals exposed as adults. Normal lung development, as reflected in the size and functional efficiency at adulthood, was not affected by NO2 in this study. Diesel exhaust altered the airway fluid constituents as well as lung tissue collagen and proteinases of both age groups. Particularly striking was an almost sixfold increase in the percentage of neutrophils, a class of highly phagocytic leukocytes, in the airway fluids of adults after six months of exposure. Exhaust-exposed adults had increased numbers of cells in pulmonary lymph nodes, delayed clearance of both diesel soot and 134Cs-labeled particles, and increased lung weight. These changes did not occur in the rats exposed during development.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗

PubMed1989

Short-term exposure to nitrogen dioxide enhances susceptibility to murine respiratory mycoplasmosis and decreases intrapulmonary killing of Mycoplasma pulmonis.

In C57BL/6N and C3H/HeN mice known to be free of all murine pathogens and matched for age, sex, microbiologic, and environmental factors, exposure to NO2 for 4 h prior to exposure to infectious aerosols of Mycoplasma pulmonis resulted in potentiation of murine respiratory mycoplasmosis (MRM). In the C57BL/6N mice, NO2 increased the incidence of death, incidence of gross lung lesions, and incidence of microscopic lung lesions, but did not increase the incidence of infection in the lungs. Nitrogen dioxide affected the C3H/HeN mice (a strain known to be more susceptible than the C57BL/6N strain to MRM) similarly, with the exception that the incidence of death and microscopic lesions were not affected in this strain at the concentrations of M. pulmonis used. Exposure to the oxidant also increased the severity of microscopic lesions and the numbers of Mycoplasma organisms in the lungs of both mouse strains. Thus, NO2 appeared to affect host lung defense mechanisms responsible for limiting the extent of infection. The NO2 exposure level required to produce potentiation varied with the genetic background of the host, the number of Mycoplasma organisms administered, and the end point measured. In further experiments in C57BL/6N mice, exposure to 5 or 10 ppm of NO2 for 4 h prior to infection with aerosolized, radiolabeled M. pulmonis reduced clearance of these organisms from the lungs over a 72-h time period. Nitrogen dioxide exposure did not change the rate of physical removal of Mycoplasma organisms from the lung. Reduced clearance was due to impaired intrapulmonary killing of Mycoplasma organisms in NO2-exposed mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1981

Chromosomal aberrations and sister-chromatid exchanges induced by gaseous nitrogen dioxide in cultured Chinese hamster cells.

Effects of gaseous nitrogen dioxide (NO2) on chromosomal morphology of cultured Chinese hamster V79-H3 cells were investigated. Chinese hamster cells were exposed to NO2 gas in N2 gas at NO2 concentrations of 0, 5, 10, 20, 50 and 100 ppm (v/v) for 10 min at a gas flow rate of 1000 ml/min. Both chromosomal aberrations and sister-chromatid exchanges were increased depending on the NO2 concentration. The effects of sodium nitrite (NaNO2) were also examined in comparison with those of gaseous NO2, and it was found that the effects of gaseous NO2 could not be ascribed to those of nitrous acid. The gas-exposure apparatus used in this experiments seems to be useful for quantitative investigation of the effects of various gaseous materials on cultured mammalian cells or bacterial cells.

Animals↗

PubMed2003

Oxidative generation of guanine radicals by carbonate radicals and their reactions with nitrogen dioxide to form site specific 5-guanidino-4-nitroimidazole lesions in oligodeoxynucleotides.

A simple photochemical approach is described for synthesizing site specific, stable 5-guanidino-4-nitroimidazole (NIm) adducts in single- and double-stranded oligodeoxynucleotides containing single and multiple guanine residues. The DNA sequences employed, 5'-d(ACC CG(1)C G(2)TC CG(3)C G(4)CC) and 5'-d(ACC CG(1)C G(2)TC C), were a portion of exon 5 of the p53 tumor suppressor gene, including the codons 157 (G(2)) and 158 (G(3)) mutation hot spots in the former sequence with four Gs and the codon 157 (G(2)) mutation hot spot in the latter sequence with two Gs. The nitration of oligodeoxynucleotides was initiated by the selective photodissociation of persulfate anions to sulfate radicals induced by UV laser pulses (308 nm). In aqueous solutions, of bicarbonate and nitrite anions, the sulfate radicals generate carbonate anion radicals and nitrogen dioxide radicals by one electron oxidation of the respective anions. The guanine residue in the oligodeoxynucleotide is oxidized by the carbonate anion radical to form the neutral guanine radical. While the nitrogen dioxide radicals do not react with any of the intact DNA bases, they readily combine with the guanine radicals at either the C8 or the C5 positions. The C8 addition generates the well-known 8-nitroguanine (8-nitro-G) lesions, whereas the C5 attack produces unstable adducts, which rapidly decompose to NIm lesions. The maximum yields of the nitro products (NIm + 8-nitro-G) were typically in the range of 20-40%, depending on the number of guanine residues in the sequence. The ratio of the NIm to 8-nitro-G lesions gradually decreases from 3.4 in the model compound, 2',3',5'-tri-O-acetylguanosine, to 2.1-2.6 in the single-stranded oligodeoxynucleotides and to 0.8-1.1 in the duplexes. The adduct of the 5'-d(ACC CG(1)C G(2)TC C) oligodeoxynucleotide containing the NIm lesion in codon 157 (G(2)) was isolated in HPLC-pure form. The integrity of this adduct was established by a detailed analysis of exonuclease digestion ladders by matrix-assisted laser desorption ionization with time-of-flight detection MS techniques.

Acetaldehyde↗

PubMed2001

Recovery from oxidant-mediated lung injury: response of metallothionein, MIP-2, and MCP-1 to nitrogen dioxide, oxygen, and ozone exposures.

Oxidant-induced lung injury is believed to be mediated by reactive oxygen species. Recovery from oxidant exposure has been associated with pulmonary inflammation. Inflammatory cell accumulation involves the synthesis of chemokines, including neutrophil chemoattractants such as macrophage inflammatory protein-2 (MIP-2) and monocyte chemoattractants such as monocyte chemoattractant protein-1 (MCP-1). Antioxidants are the first line of defense of lung cells against inhaled oxidants. Metallothionein (MT) can act as an antioxidant and free-radical scavenger. To better understand the pulmonary response associated with recovery from oxidant-mediated injury, we exposed mice to either 15 ppm nitrogen dioxide for 24 h, >99% oxygen for 72 h, or 1 ppm ozone for 24 h. Mice were examined at the end of exposure or after recovering in room air for 4 or 24 h. Neutrophils were elevated at the end of exposure and remained elevated through the postexposure period, whereas macrophage numbers were decreased at the end of exposure and remained below control levels at 4 and 24 h postexposure. MT, MIP-2, and MCP-1 mRNA levels were elevated at 4 h postexposure; however, after 24 h of recovery only MCP-1 remained elevated. These results indicate that MT, MIP-2, and MCP-1 mRNA levels responded similarly to recovery from nitrogen dioxide, oxygen, and ozone exposure. Monocyte accumulation was delayed as compared to neutrophils and was consistent with the timing of MIP-2 and MCP-1 expression. Peak expression of MT and MIP-2 preceded peak neutrophil accumulation. Consequently, the timing of MT, MIP-2, and MCP-1 expression may be important biological markers in assessing the state of injury and recovery associated with oxidant-mediated injury.

Administration, Inhalation↗

PubMed1995

Gaseous nitrogen dioxide increases the endogenous synthesis of carcinogenic N-nitrosodimethylamine in animals.

Inhalation of nitrogen dioxide (NO2) by mice administered orally amidopyrine (AP) and sodium nitrite resulted in increased biosynthesis of N-nitrosodimethylamine (NDMA), as determined by analysis using gas chromatography with thermal energy analyzer detector. These results were also confirmed indirectly in chronic experiments on rats using the system of biomarkers of NDMA formation (single-stranded DNA liver damages, alanine-aminotransferase, glutathione-S-transferase, and liver S9 fraction activity). The inhibition of NDMA metabolism by 4-methylpyrazol (4-MP) administration increases the sensitivity of NDMA biosynthesis assay in frozen whole-mouse powder. The results confirm that NO2 can serve as the precursor of nitrosamines.

Administration, Inhalation↗

PubMed1986

Induction of SOS functions by nitrogen dioxide in Escherichia coli with different DNA-repair capacities.

The effect of gaseous nitrogen dioxide (NO2) on cytotoxicity, induction of synthesis of UmuC and RecA proteins, and mutagenesis was studied in Escherichia coli strains with different capacities of DNA repair. Gaseous NO2 (90, 180 microliter/l) killed Escherichia coli. The recA mutant was most sensitive, the lexA mutant moderately sensitive, and the uvrA mutant and the wild-type the least sensitive. When 90 microliter/l NO2 gas was bubbled into bacterial suspensions for 30 min at a flow rate of 100 ml/min, the induction of umuC gene expression increased in the wild-type strain. NO2 also induced the recA gene expression in the wild-type strain. The synthesis of neither RecA nor UmuC proteins was induced in the recA and lexA mutants. We further investigated the NO2 mutagenesis in the cells treated with bubbling of NO2 gas. NO2 caused mutation to Trp+ of WP2.

DNA Repair↗

PubMed1996

Nitrogen dioxide pneumonitis in ice hockey players.

Exposure to the toxic gases carbon monoxide and nitrogen dioxide (NO2) in indoor ice arenas occasionally occurs and may result in severe symptoms. The gases are produced by ice resurfacing machines operating on hydrocarbons, and in certain conditions toxic levels accumulate. The damage to lung tissues caused by NO2 may not be evident until after a latency time of 1/2-2 days. The role of corticosteroids in the treatment is controversial, but there are clinical experiences as well as experimental data supporting their use. We report two cases of toxic pneumonitis, with delayed onset, due to NO2 exposure during an ice hockey game in an indoor arena. Signs and symptoms were cough, dyspnoea, haemoptysis, hypoxaemia and reduced peak expiratory flow. Chest radiographs showed parenchymatous infiltrative lesions and alveolar consolidation. Both patients were treated with high doses of corticosteroids by inhalation and orally or intravenously. Their condition rapidly improved and pulmonary function was restored.

Adolescent↗

PubMedDate not supplied

Does nitrogen dioxide exposure increase airways responsiveness?

A number of reports have suggested that exposure to nitrogen dioxide (NO2) may cause increased airways responsiveness (AR). Twenty studies of asthmatics and five studies of healthy subjects exposed to NO2 were used to test this hypothesis using a simple method of meta-analysis. Individual data were obtained for the above studies and the direction of change in AR was determined for each subject. Only studies with available individual data were used. Subjects from these studies whose directional change in AR could not be determined were excluded. The fraction of positive responses (i.e. increased AR) was determined for all subjects within a group and tested for significance using a sign test. Data were also grouped according to NO2 concentration and by whether the exposure included exercise. There was an overall trend among asthmatics for AR to increase (60%) but this was primarily due to increased AR seen in resting exposures (70%). Among healthy subjects AR also increased with NO2 exposure but only at concentrations above 1.0 ppm. This analysis suggests that NO2 exposure causes increased airway responsiveness in healthy and asthmatic subjects but that exercise during exposure may modify this response in asthmatics.

Asthma↗

PubMed1982

Childhood respiratory illness and the home environment. I. Relations between nitrogen dioxide, temperature and relative humidity.

The relation between the use of gas for cooking, nitrogen dioxide (NO2), temperature and relative humidity was investigated in an urban area of northern England. In a pilot study conducted in a random sample of 40 homes measurements of temperature and relative humidity were not significantly different between homes with a gas cooker and homes with an electric cooker but weekly average levels of NO2 were higher in bedrooms (p less than 0.005) and living rooms (P less than 0.01) of gas homes. In the main study conducted in gas cooking homes only, access was gained to 183 (54.3%) of 337 randomly selected homes. No correlation was found in children's bedrooms between with weekly average level of NO2 (range 4.7 to 160.8 ppb) and weekly average temperature (ranged 7.7 to 22.0 degree C; r = 0.05, p greater than 0.10) or relative humidity (range 37.0 to 98.1%; r = 0.07, p greater than 0.10). Levels of NO2 in the bedroom were positively correlated with those in the living room (range 9.0 to 292.2 ppb; r = 0.39, p less than 0.01). Factors which tended to be associated with high levels of NO2 in the home included gas fires, paraffin heaters and use of the cooker for heating and drying clothes.

Air Pollutants↗

PubMed2004

Estimation of occupational and nonoccupational nitrogen dioxide exposure for Korean taxi drivers using a microenvironmental model.

Occupational and nonoccupational personal nitrogen dioxide (NO(2)) exposures were measured using passive samplers for 31 taxi drivers in Asan and Chunan, Korea. Exposures were also estimated using a microenvironmental time-weighted average model based on indoor, outdoor and inside the taxi area measurements. Mean NO(2) indoor and outdoor concentrations inside and outside the taxi drivers' houses were 24.7+/-10.7 and 23.3+/-8.3 ppb, respectively, with a mean indoor to outdoor NO(2) ratio of 1.1. Mean personal NO(2) exposure of taxi drivers was 30.3+/-9.7 ppb. Personal NO(2) exposures for drivers were more strongly correlated with interior vehicle NO(2) levels (r = 0.89) rather than indoor residential NO(2) levels (r = 0.74) or outdoor NO(2) levels (r = 0.71). The main source of NO(2) exposure for taxi drivers was considered to be occupational driving. Interestingly, the NO(2) exposures for drivers' using LPG-fueled vehicles (26.3+/-1.3 ppb) were significantly lower than those (38.1+/-1.3 ppb) using diesel-fueled vehicle (P <0.01). Since drivers spent most of their time inside their vehicle and indoors at home, a microenvironmental model was used to estimate the personal NO(2) exposure with indoor and outdoor NO(2) levels of the residence, and interior vehicle NO(2) levels (P <0.001). Some subpopulations, such as professional drivers, might be exposed to high NO(2) levels because they drive diesel-using vehicles outdoors in Korea.

Adult↗

PubMed1987

Influence of exposure patterns of nitrogen dioxide and modifications by ozone on susceptibility to bacterial infectious disease in mice.

The nitrogen dioxide (NO2) diurnal cycle found in urban communities usually consists of a low basal concentration upon which are superimposed higher concentration peaks or spikes of short duration. Various components of this environmental exposure mode were examined to assess effects of urban exposure profiles on susceptibility to infectious pulmonary disease. Mice were exposed to NO2 peaks of 4.5 ppm for 1, 3.5, or 7 h, challenged with Streptococcus sp. either immediately or 18 h postexposure, and then observed for mortality. When the streptococcal challenges were immediately after NO2 exposure, the mortality rate was directly related to the length of peak exposure, whether or not a basal exposure was used, and all peak lengths significantly increased mortality. When the challenge was delayed for 18 h after the peak exposure, spiked exposures of 3.5 and 7 h increased mortality to the same degree. If a 1-h peak exposure to 4.5 ppm was superimposed twice daily upon a continuous basal NO2 concentration of 1.5 ppm, there was a suggestive trend toward increased mortality near the end of the second week of exposure when challenge occurred immediately after the morning spike. Studies were also conducted to examine interactions with ozone (O3) and NO2, since urban air typically contains both of these oxidants. Using various combinations of basal and spiked exposure levels of NO2 and O3, synergistic results were obtained for streptococcal-induced mortality.

Air Pollutants↗

PubMed1981

Lung injury and repair in the blotchy mouse. Effects of nitrogen dioxide inhalation.

We studied the reparative process after inhalation exposure to 20 ppm of nitrogen dioxide (NO2) in the lungs of hemizygous blotchy male (Blo/g) and heterozygous blotchy female (Bio/+) mice. Age-matched siblings (C3Hf) without the blotchy gene at X-chromosome locus (+/y) and +/+) served as control animals. After exposure to NO2 for 28 days, there was a marked progression in the extent of emphysema in Blo/y mice associated with a significant decrease of internal surface area (p < 0.05) and an increase in the mean linear intercept (p < 0.005). In contrast, +/y, Blo/+, and +/+ mice showed mild airspace enlargement without decrease in internal surface area after similar exposures. Blo/y mice killed 1 month after cessation of NO2 exposure showed a persistent, mild chronic bronchiolitis that was more frequent and of greater severity than that present in control +/y mice. Alveolar macrophages in the Blo/y mice were larger than those in +/y, +/+, and Blo/+ mice both before and after exposure to NO2. Crystalloid inclusions were observed in the enlarged alveolar macrophages of the Blo/g mice only after exposure to NO2, but were not seen in control animals. These observations indicate that the pattern of lung injury and repair after subacute exposure to 20 ppm of NO2 in the Blo/y mouse differs from that present in age-matched siblings in that inherited abnormalities in alveolar macrophage function may exist in addition to the previously described alterations in connective tissue proteins. Both of these alterations may influence the development of emphysema in the blotchy male mouse.

Animals↗

PubMed1996

Nitrogen dioxide causes pulmonary arterial relaxation via thiol nitrosation and NO formation.

Micromolar concentrations of nitrogen dioxide (NO2), a key metabolite of nitric oxide (NO) and peroxynitrite (ONOO-), were observed to cause a prolonged relaxation of isolated endothelium-removed rings of bovine pulmonary arteries (BPA) precontracted with 30 mM potassium. Relaxation to NO2 was markedly inhibited by 1 microM hemoglobin (Hb), 10 microM methylene blue (MB), and 10 microM LY-83583. The response to NO2 was enhanced in the presence of 1 mM reduced glutathione (GSH) or cysteine. The addition of NO2 to Krebs bicarbonate buffer (under 95% N2-5% CO2) containing 1 mM GSH or BPA resulted in an increase in NO formation (measured in head space gas). Relaxation to NO2 and NO formation were markedly decreased after GSH depletion by pretreatment of BPA with diethyl maleate. A high-performance liquid chromatography analysis of the products formed immediately after the addition of NO2 to GSH detected a previously isolated (but not identified) potent relaxing agent formed by a reaction of GSH with ONOO-, and this material comigrated with a synthetic product thought to be S-nitro-GSH (GSNO2). Nanomolar concentrations of GSNO2 caused a potent dose-dependent relaxation that was inhibited by Hb, MB, and LY-83583. Therefore NO2 appears to cause a prolonged guanosine 3',5'-cyclic monophosphate-mediated relaxation in BPA via thiol nitration and a subsequent time-dependent release of NO. Thus NO2 (and ONOO-) may function in a tissue hormonelike regulatory role in inflammatory processes in which large amounts of these species are produced.

Animals↗

PubMed2002

Nitrogen dioxide exposure: effects on airway and blood cells.

This study examined the effects of nitrogen dioxide (NO(2)) exposure on airway inflammation, blood cells, and antiviral respiratory defense. Twenty-one healthy volunteers were exposed on separate occasions to air and 0.6 and 1.5 ppm NO(2) for 3 h with intermittent moderate exercise. Phlebotomy and bronchoscopy were performed 3.5 h after each exposure, and recovered cells were challenged with respiratory viruses in vitro. Blood studies revealed a 4.1% NO(2) dose-related decrease in hematocrit (P = 0.003). Circulating total lymphocytes (P = 0.024) and T lymphocytes (P = 0.049) decreased with NO(2) exposure. Exposure to NO(2) increased the blood lymphocyte CD4(+)-to-CD8(+) ratio from 1.74 +/- 0.11 to 1.85 +/- 0.12 in males but decreased it from 1.88 +/- 0.19 to 1.78 +/- 0.19 in females (P < 0.001 for gender difference). Polymorphonuclear leukocytes in bronchial lavage increased with NO(2) exposure (P = 0.003). Bronchial epithelial cells obtained after exposure to 1.5 ppm NO(2) released 40% more lactate dehydrogenase after challenge with respiratory syncytial virus than with air exposure (P = 0.024). In healthy subjects, exposures to NO(2) at levels found indoors cause mild airway inflammation, effects on blood cells, and increased susceptibility of airway epithelial cells to injury from respiratory viruses.

Adult↗

PubMed1997

Nitrogen dioxide exposure activates gamma-glutamyl transferase gene expression in rat lung.

Exposure to nitrogen dioxide (NO2) has been shown to activate glutathione metabolism in lung and lung lavage. Since GGT is a key enzyme in glutathione metabolism and we have previously characterized GGT expression in distal lung epithelium and in lung surfactant, we examined the NO2 exposed lung for induction of gamma-glutamyl transferase (GGT) mRNA, protein, and enzyme activity. We found that the GGT gene product is induced in lung by NO2. The GGT mRNA level in lung increases 2-fold within 6 hr and 3-fold after 24 hr of exposure to this oxidant gas, and this 3-fold elevation persists even after 14 days of exposure. The pattern of GGT mRNA expression switches from the single GGT mRNA III transcript in the normal lung to the dual expression of GGT mRNA I and mRNA III. Enzyme activity in whole lung increases 1.6- to 2.5-fold while extracellular surfactant-associated GGT activity accumulates 5.5-fold and GGT protein accumulates in lung surfactant. Induction of GGT mRNA and protein is evident in cells of the bronchioles by in situ hybridization and immunolocalization, respectively. In contrast, alveolar type 2 cells lack an in situ hybridization signal and exhibit a reduction in the intensity of immunostaining with prolonged exposure. Our studies show that NO2 induces GGT mRNA expression, including GGT mRNA1, in lung and GGT protein and enzyme activity in lung and lung lavage in response to the oxidative stress of NO2 inhalation.

Administration, Inhalation↗