Gary E Hatch

Gary E Hatch
United States Environmental Protection Agency | US EPA · Office of Research and Development

Ph.D.

About

131
Publications
11,493
Reads
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5,802
Citations
Introduction
Dr. Hatch retired from a 38-year career investigating the biochemistry of the respiratory tract and how it responds to air pollutant exposure, infections and allergies. Through examination of nasal and pulmonary lavage fluids from animals and humans, he created important linkages between human and animal data to assist in extrapolating results from laboratory animals to humans. He has pioneered new methods to understand factors such as diet and exercise that lead to increased susceptibility t
Additional affiliations
July 1979 - present
United States Environmental Protection Agency
Position
  • Research Biologist
January 1977 - July 1979
Duke University
Position
  • Postdoctoral
July 1973 - January 1977
University of Utah
Position
  • PhD Student

Publications

Publications (131)
Article
Full-text available
Inhaled ozone (O3) reacts chemically with respiratory tract biomolecules where it forms covalently bound oxygen adducts. We investigated the fate of these adducts following inhalation exposure of rats to labeled ozone ((18)O3, 2 ppm, 6 hr or 5 ppm, 2 hr). Increased (18)O was detected in blood plasma at 7 hr post exposure and was continuously presen...
Article
Full-text available
To determine the influence of exercise on pulmonary dose of inhaled pollutants, we compared biomarkers of inhaled ozone (O3) dose and toxic effect between exercise levels in humans, and between humans and rats. Resting human subjects were exposed to labeled O3 ((18)O3, 0.4 ppm, for 2 hours) and alveolar O3 dose measured as the concentration of exce...
Article
Ozone exposure effect on free radical-catalyzed oxidation products of lipids, proteins and DNA in the plasma and urine of rats was studied as a continuation of the international Biomarker of Oxidative Stress Study (BOSS) sponsored by NIEHS/NIH. The goal was to identify a biomarker for ozone-induced oxidative stress and to assess whether inconsisten...
Article
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Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the US and its impact continues to increase in women. Oxidant insults during critical periods of early life appear to increase risk of COPD through-out the life course. To better understand susceptibility to early life exposure to oxidant air pollutants we used Fish...
Article
Full-text available
We examined the hypothesis that antioxidant substances and enzymes in lung, heart and in bronchoalveolar lavage fluid (BALF) are altered in response to O3 in cardiovascular disease and/or metabolic syndrome (CVD)-prone rat models. CVD strains [spontaneously hypertensive (SH), SH stroke-prone (SHSP), SHHF/Mcc heart failure obese (SHHF), insulin-resi...
Article
This is the newest report in a series of publications aiming to identify a blood-based antioxidant biomarker that could serve as an in vivo indicator of oxidative stress. The goal of the study was to test whether acutely exposing Göttingen mini pigs to the endotoxin lipopolysaccharide (LPS) results in a loss of antioxidants from plasma. We set as a...
Article
Full-text available
In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was t...
Article
Full-text available
One of the most vital of the cellular defenses against pollution is an antioxidant armanentarium which consists of oxidant scavenging molecules such as vitamin E, glutathione, vitamin C, and uric acid as well as a number of enzymes (superoxide dismutase, semidehydroascorbate reductase, catalase, GSH synthetase, GSH peroxidase, GSH reductase, and GS...
Data
Levels of 18O measured in urine following intratracheal instillation of bovine serum albumin or phosphatidyl choline that had been pre-labeled with 18O by in vitro bubbling of 18O3 through the solution. See Table 2 for estimation of 18O recovery in urine. We were unable to perform the usual statistical analysis of the delta values on these samples...
Data
Urinary creatinine concentrations of rats pre- and post exposure to 18O3, 5 ppm, 2 hr. Effects are similar to those seen with urea in the previous figure.
Data
Urinary urea concentrations of rats pre- and post exposure to 18O3, 5 ppm, 2 hr. Exposure to both air and 18O3 resulted in more concentrated urine due apparently to stress induced by individual housing in wire mesh exposure cages.
Data
Effect of a pre-exposure to O3 (5 ppm, 2 hr) one week previous to an exposure to 18O3 (5 ppm, 2 hr). Mean values of 18O concentration taken at the morning time were plotted along with their respective equations and R values of logarithmic trend lines. Note that the pre-exposure had a minimal effect on the washout curve of 18O in the urine.
Data
The effect of heating dried urine samples to temperatures up to 500 °C. Note that dry weight was decreased at lower temperatures than 18O content. The appearance of the residues was as follows: 250 °C, black, 300 °C–400 °C, light gray turning to brown after cooling, 500 °C, white.
Article
We assessed the feasibility of marking ruby-throated hummingbirds (Archilochus colubris) with radio frequency identification (RFID) tags. We trapped 27 hummingbirds at feeding stations on a 2.0-ha study site. We subcutaneously implanted each hummingbird with a 0.067-g RFID tag and released it at the capture site. We deployed RFID transceiver system...
Article
The objective of this study was to determine whether acutely exposing rats to ozone would result in the loss of antioxidants from plasma and bronchoalveolar lavage fluid (BALF). Additional goals were to compare analyses of the same antioxidant concentration between different laboratories, to investigate which methods have the sensitivity to detect...
Article
Full-text available
Ozone (O(3)) is a respiratory irritant that leads to airway inflammation and pulmonary dysfunction. Animal studies show that neonates are more sensitive to O(3) inhalation than adults, and children represent a potentially susceptible population. This latter notion is not well established, and biological mechanisms underlying a predisposition to pol...
Article
Full-text available
Oxidative stress plays a significant role in allergic airway inflammation. Supplementation with alpha-tocopherol (alone or combined with ascorbate/vitamin C) has been assessed as an intervention for allergic airway diseases with conflicting results. Enhancing levels of airway antioxidants with oral supplements has been suggested as an intervention...
Article
Full-text available
Ozone O3 has been postulated to induce DNA damage and has been shown to be mildly tumorigenic in some studies utilizing long-term rodent exposures. We investigated lung DNA damage induced by controlled O3 exposure in vivo in guinea pigs and human subjects. We specifically examined DNA single-strand breaks SSB using the single-cell gel electrophores...
Article
Full-text available
Epidemiologic studies have associated exposures to air pollution particles with human mortality. Much of this excess mortality is attributed to a respiratory injury. It has been postulated that such injury after particle exposure can result from the capacity of these dusts to catalyze the generation of oxygen-based free radicals. We tested the stud...
Article
Full-text available
Abstract Questions about the adequacy of the existing ozone (O3)standard prompted an examination of relationships between concentration (C) and exposure time (T) and the impact of changes in the C × T product on toxic responses. Using protein concentration of bronchoalveolar lavage fluid (BALP) as an index of O3-induced lung damage, models were dev...
Article
Full-text available
Abstract The effect of depleting lung ascorbic acid (AH2) and nonprotein sulfhydryls (NPSH) on the acute inhalation toxicity of nitrogen dioxide (NO2), ozone (O3), and phosgene (COCl2) was investigated in guinea pigs. The increase in bronchoalveolar lavage (BAL) fluid protein (an indicator of alveolar-capillary damage leading to increased permeabil...
Article
Full-text available
Abstract Acute exposure to phosgene, a toxic gas widely used in industrial processes, decreases resistance to bacteria in mice and rats and enhances susceptibility to B16 tumor cell challenge in mice. These effects appear to be due to impaired alveolar macrophage and natural killer (NK) cell activity, respectively. In this study effects of repeated...
Article
Increases in Clara cell abundance or cellular expression of Clara cell secretory protein (CCSP) may cause increased tolerance of the lung to acute oxidant injury by repeated exposure to ozone (O3). This study defines how disruption of the gene for CCSP synthesis affects the susceptibility of tracheobronchial epithelium to acute oxidant injury. Mice...
Article
Potassium bromate (KBrO3) is a chemical oxidizing agent found in drinking water as a disinfection byproduct of surface water ozonation. Chronic exposures to KBrO3 cause renal cell tumors in rats, hamsters and mice and thyroid and testicular mesothelial tumors in rats. Experimental evidence indicates that bromate mediates toxicological effects via t...
Article
Full-text available
Ozone is an oxidant gas that can directly induce lung injury. Knowledge of the initial molecular events of the acute O3 response would be useful in developing biomarkers of exposure or response. Toward this goal, we exposed rats to toxic concentrations of O3 (2 and 5 ppm) for 2 hr and the molecular changes were assessed in lung tissue 2 hr postexpo...
Article
Full-text available
Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent m...
Article
The inflammatory response to ozone in atopic asthma suggests that soluble mediators of inflammation are released in response to oxidant stress. Antioxidants may alleviate additional oxidative stress associated with photochemical oxidant pollution. This study investigates the impact of antioxidant supplementation on the nasal inflammatory response t...
Article
Full-text available
We examined the effect of breathing pattern on ozone reaction product content within the respiratory tract. Thirty-four anesthetized, male Wistar rats were exposed to oxygen-18 ((18)O)-labeled ozone at 1.0 ppm for 2 h using a dual-chamber, negative-pressure ventilation system. Frequency was set at 80 (n = 9), 120 (n = 7), 160 (n = 8), or 200 (n = 1...
Article
Full-text available
Brown Norway (BN) rats develop a robust response to antigens in the lung, characterized by a large increase in allergen-specific immune function and pulmonary eosinophilia. The objective of this study was to investigate alternative models by determining whether other rat strains could be sensitized to house dust mite (HDM) antigen and whether the a...
Article
Full-text available
Asthma is primarily an airways inflammatory disease, and the bronchial airways have been shown to be particularly susceptible to oxidant-induced tissue damage. The antioxidant ascorbic acid (AA) plays an essential role in defending against oxidant attack in the airways. Decreased levels of AA have been reported in the plasma and BAL fluid of asthma...
Article
Full-text available
To evaluate whether acute effects of ozone, nitrogen dioxide, and particulates with mass median diameter less than 10 micro m could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blinded design. Children with asthma (n = 158) who were residents of Mexico City were randomly given a daily suppleme...
Article
Full-text available
Epidemiology studies show association of morbidity and mortality with exposure to ambient air particulate matter (PM). Metals present in PM may catalyze oxidation of important lipids and proteins present in the lining of the respiratory tract. The present study investigated the PM-induced oxidation of human bronchoalveolar lavage (BAL) fluid (BALF)...
Article
Full-text available
To determine whether antioxidants can influence human susceptibility to ozone (O(3))-induced changes in lung function and airway inflammation, we placed 31 healthy nonsmoking adults (18 to 35 yr old) on a diet low in ascorbate for 3 wk. At 1 wk, subjects were exposed to filtered air for 2 h while exercising (20 L/min/m(2)), and then underwent bronc...
Article
Full-text available
The present study compares acute and subchronic episodic exposures to phosgene to test the applicability of the 'concentrationxtime' (CxT) product as a measure of exposure dose, and to relate acute toxicity and adaptive responses to chronic toxicity. Rats (male Fischer 344) were exposed (six hours/day) to air or 0.1, 0.2, 0.5 and 1.0 ppm of phosgen...
Article
Full-text available
Inhaled urban particulate matter (PM) often contains metals that appear to contribute to its toxicity. These particles first make contact with a thin layer of epithelial lining fluid in the respiratory tract. Antioxidants present in this fluid and in cells might be important susceptibility factors in PM toxicity. We investigated the role of ascorbi...
Article
Full-text available
Ambient particulate matter (PM) concentrations have been associated with mortality and morbidity. Diesel exhaust particles (DEP) are present in ambient urban air PM. Coexisting with DEP (and PM) is ozone (O(3)), which has the potential to react with some components of DEP. Some reports have shown increased lung injury in rats coexposed to PM and O(...
Article
Cardiovascular disease is considered a probable risk factor of particulate matter (PM)-related mortality and morbidity. It was hypothesized that rats with hereditary systemic hypertension and underlying cardiac disease would be more susceptible than healthy normotensive rats to pulmonary injury from inhaled residual oil fly ash (ROFA) PM. Eight spo...
Article
Full-text available
The evaluation of respiratory tract toxicity from airborne materials frequently involves exposure of animals via inhalation. This provides a natural route of entry into the host and, as such, is the preferred method for the introduction of toxicants into the lungs. However, for various reasons, this technique cannot always be used, and the direct i...
Article
Full-text available
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace environmental contaminant and is one of the most potent toxicants known to man. Hassoun et al. (1998, Toxicol. Sci. 42, 23-27) reported an increase in the production of reactive oxygen species (ROS) in the brain of female B6C3F1 mice following subchronic exposure to TCDD at dos...
Article
Antioxidants in the blood plasma of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. For this initial study an animal model of CCl(4) poisoning was studied. The time (2, 7, and 16 h) and dose (120 and 1200 mg/kg, intraperitoneally)-dependent effects of CCl(4) o...
Article
1.Ozone (O3) inhalation induces a hypothermic response in rodents characterized primarily by core body temperature (TCO) and heart rate (HR) decreases.2.This preliminary study examined TCO, HR, and electrocardiographic changes in rats and guinea pigs during whole-body or nose-only exposure to 1 ppm 18O3.3.Rats exposed whole-body demonstrated an imm...
Article
Full-text available
Nitrogen dioxide (NO2) is a common indoor air pollutant, especially in homes with unvented combustion appliances. Epidemiological studies suggest that children living in homes with unvented heating sources are more prone to respiratory infections than children living in homes with lower levels of NO2. However, experimental studies in which human vo...
Article
Full-text available
Previous studies have shown that rats late in pregnancy and throughout lactation are more susceptible to ozone (O3)-induced pulmonary inflammation than are prepregnant (virgin) or postlactating rats. The major aim of the present study was to determine whether these differences in response intensity could be accounted for by the O3 dose to the lower...
Article
Full-text available
Acute pulmonary epithelial injury produced by short-term exposure to ozone varies by site within the tracheobronchial tree. To test whether this variability is related to the local dose of ozone at the tissue site or to local concentrations of glutathione, we exposed adult male rhesus monkeys for 2 h to filtered air or to 0.4 or 1.0 ppm ozone gener...
Article
Full-text available
Epidemiologic studies have shown significant associations between ambient particulate matter (PM) levels and a variety of human health endpoints. This study examined the cellular and biochemical effects in normal and antioxidant deficient guinea pigs (GP) after exposure to residual oil fly ash (ROFA) obtained from a power plant (15-20 mg/m3 of PM2....
Article
Full-text available
Exposures of the lung to iron chelates can be associated with an injury. The catalysis of oxygen-based free radicals is postulated to participate in this injury. Such oxidant generation by mineral oxide particles can be dependent on availability of both iron and a reductant. We tested the study hypothesis that lung injury after silica is associated...
Article
Full-text available
Studies were undertaken to determine whether dietary restriction protects against acute pulmonary oxidant challenge. Male F344 rats were fed NIH-31 diet either ad libitum or at restricted levels equal to 75% that of ad libitum intake. After 3 wk of dietary adaptation, animals were exposed by inhalation to 2.0 ppm ozone (O3) for 2 h or chamber air a...
Article
Macrophages and inflammatory cells generate active oxygen species in the process of killing and degrading microorganisms. Air pollutant particles may be ingested by macrophages and stimulate the same mechanisms to produce a long term oxidative burden to the lung if particles are not degraded. In the present study human and rat alveolar macrophages...
Article
Full-text available
Ozone (O3) has been postulated to induce DNA damage and has been shown to be mildly tumorigenic in some studies utilizing long-term rodent exposures. We investigated lung DNA damage induced by controlled 03 exposure in vivo in guinea pigs and human subjects. We specifically examined DNA single-strand breaks (SSB) using the single-cell gel electroph...
Article
Phosgene, an acylating agent, is a very potent inducer of pulmonary edema. Subchronic effects of phosgene in laboratory animals are not well characterized. The purpose of the study was to elucidate potential long-term effects on collagen and elastin metabolism during pulmonary injury/recovery and obtain information about the concentration x time (C...
Article
Full-text available
Humans exposed to ozone a single time develop decrements in lung function and an inflammatory reaction in the lung characterized by increased numbers of neutrophils and increased amounts of soluble mediators of inflammation such as interleukin (IL)-8, IL-6, prostaglandin (PG) E2, lactate dehydrogenase, elastase, and lung protein in bronchoalveolar...
Article
Full-text available
Strain differences in susceptibility to inhaled ozone (O3) have been observed in mice, with C57BL/6J (B6) mice reported to be more sensitive than C3H/HEJ (C3) mice when exposed to equal concentrations of O3. To determine whether differences in the delivered dose of O3 to the lung could help explain these differences, C3 and B6 mice were exposed to...
Article
Full-text available
Epidemiologic studies have associated exposures to air pollution particles with human mortality. Much of this excess mortality is attributed to a respiratory injury. It has been postulated that such injury after particle exposure can result from the capacity of these dusts to catalyze the generation of oxygen-based free radicals. We tested the stud...
Article
Full-text available
Biological effects indicators in bronchoalveolar lavage fluid were studied in Fischer 344 rats of different ages after exposure to 0.4-0.8 ppm ozone for periods of 2-6 h on a single day or on 4 consecutive days. The magnitude of alveolar protein transudation induced by ozone was not different between age groups, but the interindividual variability...
Article
Full-text available
Lung exposures to complexes of coordinated iron can be associated with a neutrophilic alveolitis. We tested the hypothesis that lung inflammation after intratracheal instillation of mineral oxides in rats increases with surface-complexed [Fe3+]. The 10 mineral oxides employed had measurable [Fe3+] complexed to the dust surface. The metal was incomp...
Article
Evidence to explain the enhanced hepatotoxicity of carbon tetrachloride (CCl4) following methanol exposure by inhalation is presented. Hepatic microsomes prepared from male F344 rats exposed to methanol at concentrations up to 10,000 ppm showed increased p-nitrophenol hydroxylase activity but no increase in pentoxyresorufin-O-dealkylase or ethoxyre...
Article
Full-text available
Studies from this laboratory have shown that lactating rats exhibit a greater inflammatory response to inhaled ozone than age-matched nulligravidous or postlactating rats. One factor contributing to this enhanced response by lactating rats is their greater ventilation, which results in a higher inhaled dose rate. In the study reported here, we inve...
Article
Full-text available
Previous studies have indicated that systemic deficiency in one of the critical antioxidants, ascorbate, does not significantly exacerbate ozone-induced lung injury and changes in lung antioxidants following longer-term exposure. Because alveolar cells encounter the highest ozone dose upon exposure and lack direct blood supply, systemic ascorbate d...
Article
Full-text available
Previous studies from this laboratory have demonstrated a concentration-related hypothermia and increases in bronchoalveolar lavage (BAL) fluid indexes of toxicity in the rat after exposure to environmentally relevant levels of ozone (O3). In similar studies with C57BL/6J (B6) and C3H/HeJ (C3) mice, other investigators have reported differential ef...
Article
Acute exposure of humans to ozone results in reversible respiratory function decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and bio...
Article
Full-text available
Exposures to 100% oxygen, ozone, nitrogen oxides, and phosgene increase both lung lavage protein concentrations and neutrophils. The inhibition of the neutrophil influx can diminish lavage protein concentrations after exposures to these oxidant gases. Similarly, this injury can be reduced by pre-exposure to either the same (tolerance) or a differen...
Article
Strain differences in susceptibility to inhaled ozone (03) have been reported in mice, with C57BL/6J (B6) mice more sensitive than C3H/HEJ (C3) mice as measured by increased bronchoalveolar lavage fluid (BALF) protein concentrations. In order to determine whether differences in the delivered dose of 03 to the lung could explain these strain differe...
Article
It has been reported previously that ozone (O3) toxicity from acute (4 hr) exposure is enhanced by ascorbate (AH2) deficiency in guinea pigs. We hypothesized that lung injury from continuous 1-week O3 exposure would also be increased under conditions of AH2 deficiency because of (1) a diminished antioxidant pool to counteract the oxidant challenge,...
Article
Full-text available
The possible influence of dietary antioxidants, especially vitamin C, on the increasing prevalence of asthma is explored. Vitamin C intake in the general population appears to correlate with asthma, suggesting that a diet low in vitamin C is a risk factor for asthma. Epidemiological studies show associations among oxidant exposure, respiratory infe...