Biomedical subjects

Lung-Chi Chen

Publications and source records attributed to Lung-Chi Chen.

5 recordsLinked to original sources

PubMed2006

Cardiovascular effects of nickel in ambient air.

BACKGROUND: Fine particulate matter (FPM) in ambient air causes premature mortality due to cardiac disease in susceptible populations. OBJECTIVE: Our objective in this study was to determine the most influential FPM components. METHODS: A mouse model of atherosclerosis (ApoE-/-) was exposed to either filtered air or concentrated FPM (CAPs) in Tuxedo, New York (85 microg/m3 average, 6 hr/day, 5 days/week, for 6 months), and the FPM elemental composition was determined for each day. We also examined associations between PM components and mortality for two population studies: National Mortality and Morbidity Air Pollution Study (NMMAPS) and Hong Kong. RESULTS: For the CAPs-exposed mice, the average of nickel was 43 ng/m3, but on 14 days, there were Ni peaks at approximately 175 ng/m3 and unusually low FPM and vanadium. For those days, back-trajectory analyses identified a remote Ni point source. Electrocardiographic measurements on CAPs-exposed and sham-exposed mice showed Ni to be significantly associated with acute changes in heart rate and its variability. In NMMAPS, daily mortality rates in the 60 cities with recent speciation data were significantly associated with average Ni and V, but not with other measured species. Also, the Hong Kong sulfur intervention produced sharp drops in sulfur dioxide, Ni, and V, but not other components, corresponding to the intervention-related reduction in cardiovascular and pulmonary mortality. CONCLUSIONS: Known biological mechanisms cannot account for the significant associations between Ni with the acute cardiac function changes in the mice or with cardiovascular mortality in people at low ambient air concentrations; therefore, further research is needed.

Air Pollutants↗

PubMed2005

PM source apportionment for short-term cardiac function changes in ApoE-/- mice.

Daily rates of cardiovascular mortality and morbidity are have been associated with daily variations in fine particulate matter (aerodynamic diameter < or = 2.5 microm, PM2.5), but little is known about the influences of the individual source-related PM2.5 categories or the temporal lags for the effects. We investigated heart rate (HR) and HR variability (HRV) data collected during a 5-month study involving 6 hr/day, 5 day/week exposures of normal (C57) mice and a murine model for atherosclerotic disease (ApoE-/-) in Sterling Forest (Tuxedo, New York, USA). The mice were exposed to concentrated ambient particles (PM2.5 concentrated 10-fold, producing an average of 113 microg/m3). Daily 6-hr PM2.5 air samples were analyzed by X-ray fluorescence, permitting attribution to major PM source categories [secondary sulfate (SS), resuspended soil (RS), residual oil (RO) combustion, and other, largely due to motor vehicle traffic]. We examined associations between these PM2.5 components and both HR and HRV for three different daily time periods: during exposure, the afternoon after exposure, and late at night. For HR there were significant transient associations for RS during exposure, and for SS in the afternoon after exposure. For HRV, there were comparable associations with RO in the afternoon after exposure and for both SS and RS late at night. The biologic bases for these associations and their temporal lags are not known but may be related to the differential solubility of the biologically active PM components at the respiratory epithelia and their access to cells that release mediators that reach the cardiovascular system. Clearly, further research to elucidate the underlying processes is needed.

Air Pollutants↗

PubMed2003

Impact of coexposure to ozone on the carcinogenic potential of inhaled chromium. 1. effects on retention and on extra- and intracellular distribution.

A health hazard to welders is development of lung cancer. It is believed that this is likely due, in part, to the presence in welding fumes of several hexavalent chromium (Cr[VI]) species, whose solubility depends primarily on which process (i.e., manual metal arc verus metal-inert gas) is used. However, inhalation of Cr alone is uncommon in this setting. Thus, an examination of potential contributions from other coinhalants in creating or enhancing conditions whereby inhaled fume-associated Cr (primarily the insoluble forms) may initiate cancer is critical to increasing our understanding and preventing this particular occupational disease. One major chemical species formed and released during welding is ozone (O3). Though implications of adverse pulmonary effects from individual exposure to Cr or O3 have been investigated, those from simultaneous exposure are unclear. To begin to address whether the carcinogenic potential of insoluble Cr[VI] agents might be enhanced in hosts inhaling mixtures of Cr and O3 versus Cr alone, analyses of total lung Cr burden, Cr retention in lung epithelium and interstitium, and potential shifts in lung cell distribution of Cr from the cytoplasm to nuclei were undertaken in F-344 rats exposed nose-only (5 h/d, 5 d/wk for up to 48 wk) to an extrapolated occupationally relevant level of Cr (360 micrograms Cr/m3 as calcium chromate) alone and in combination with 0.3 ppm O3. Overall, there was only a nominal effect from O3 on Cr retention or on distribution of Cr particles among extracellular sites and within lung cells. However, there were O3-related effects upon mechanisms for clearing the Cr from the deep lung, specifically at the levels of particle uptake and postphagocytic/endocytic processing by macrophages. This O3 exposure-related shift in normal pulmonary clearance might potentially increase the health risk in workers exposed to other insoluble or poorly soluble carcinogenic Cr compounds.

Administration, Inhalation↗

PubMed2002

Albumin adducts of benzene oxide and 1,4-benzoquinone as measures of human benzene metabolism.

Albumin adducts of benzene oxide (BO-Alb) and 1,4-benzoquinone (1,4-BQ-Alb) were investigated among 134 workers exposed to benzene and 51 unexposed controls in Tianjin, China. Concentrations of both adducts increased with benzene exposure [range = 0.07-46.6 parts/million (ppm); median = 3.55 ppm] and with urinary cotinine. Adduct levels were less than proportional to benzene exposure, suggesting saturable CYP 2E1 metabolism of benzene. Because the transition from linear to saturable metabolism began at approximately 1 ppm, the common assumption of linear kinetics at much higher benzene exposures could lead to substantial underestimation of leukemia risks. Adduct levels were generally lower in older workers, indicating that CYP 2E1 metabolism diminished with age, at approximately 2%/year of life. The ratio of 1,4-BQ-Alb:BO-Alb decreased with age and coexposure to toluene, and increased with alcohol consumption. This indicates that factors affecting CYP 2E1 metabolism exerted a greater role on production of 1,4-BQ than BO, presumably because of the second oxidation step from phenol to hydroquinone. The adduct ratio was also positively associated with urinary cotinine, suggesting that both benzene and hydroquinone from cigarette smoke affected adduct levels. Results of a limited time course study of 11 subjects indicated moderate chemical instability of 1,4-BQ-Alb (half life = 13.5 days compared with 21 days for normal Alb turnover), whereas no evidence of instability of BO-Alb was observed. This study illustrates that Alb adducts can be used to investigate the dispositions of reactive metabolites of procarcinogens in humans, provided that exposures are adequately characterized in the month preceding blood collection.

Adolescent↗

PubMed2002

Rapid communication: effect of inhaled chromium on pulmonary A1AT.

A major health hazard to coal miners is development of emphysema following long-term exposure to coal dust. One mechanism underlying development of emphysema is the oxidation of critical methionine (Met) residues in antiproteolytic factor, alpha1-antitrypsin (A1AT) resulting in a protease-antiprotease imbalance in the lung. Several studies have documented an association between the incidence and severity of emphysema among miners and their exposure to crystalline silica (i.e., SiO(2)). However, what remains unclear is the role of other co-inhaled nonemphysematogenic nonoxidant inorganic constituent in disease pathogenesis. We hypothesize that in miners, inhaled trivalent chromium (Cr(3+), the only form of Cr in coal) may potentially affect lung A1AT activity in situ via Cr complexing with Met residues, and thereby exacerbate any SiO(2)-induced imbalance. To ascertain if Cr(3+) could, in fact, affect A1AT activity, in vitro studies were done to assess elastase inhibitory activity following A1AT incubation with soluble Cr(3+). In addition, to determine if Cr(3+) found in the lungs as detoxification products of inhaled hexavalent Cr (Cr(6+)) could affect A1AT in situ, lavages from the lungs of chromate-exposed rats were also analyzed for elastase inhibitory activity The in vitro results indicate that Cr(3+) ions clearly inhibited A1AT function, with an IC50 of 1.1 mM being estimated under the experimental conditions used. The in vivo results indicate that long-term inhalation (12 wk or longer) of chromate-bearing atmospheres also gave rise to significant (i.e., 50-70%) inhibition of the antielastase activity of A1AT. Together, these results clearly suggest that the Cr(3+) present in coal dusts could potentially act to inhibit A1AT activity in the lungs of miners and thereby promote the emphysematogenicity of SiO(2) or of other emphysematogens present as coconstituents in these dusts.

Administration, Inhalation↗