Extramural Research
Research Centers
Grantee Research Project Results
Günter Oberdörster, Director
University of Rochester, Rochester, NY
EPA Grant Number: R827354
Center Overview:
The Rochester Center is comprised of five Research Cores, which focus on the hypothesis that ambient ultrafine particles (UFP) cause adverse health effects. Studies reflect a highly integrated approach linking measurement and physicochemical characterization of ambient ultrafine and fine PM (Core 1) with (i) epidemiological findings (Core 2) from panel studies in susceptible populations, including patients with coronary heart disease and patients with COPD; (ii) results of controlled clinical exposures (Core 3) of healthy and asthmatic subjects exposed to ultrafine carbon particles; (iii) outcomes of studies in aged rats and a mouse model of neurodegeneration (Core 4) following exposures to ultrafine carbon particles and on-road highway aerosols; and (iv) findings from in vitro studies (Core 5) to evaluate underlying mechanisms of injury that will explain in vivo findings. The Research Cores are supported by four Facility Cores: Aerosol Generation, Vascular, Cardiac, and Biostatistics, which are essential elements in our coordinated research approach.
Findings of the Rochester PM Center include:
Ambient ultrafine/fine particles:
• Have reactive oxygen species (ROS) so that, in addition to the potential for particulate constituents induc- ing the formation of ROS in the respiratory tract, the particles bring such materials to the tissues due to their composition (Venkatachari et al., 2004);• Are associated with changes in vascular parameters indicative of an acute phase response, increased co- agulation activation and adhesion molecule expression in patients with coronary heart disease (Rückerl et al., 2004);
• Are associated with onset of myocardial infarction 1 hr after exposure to traffic, according to time activity diaries (Peters et al., 2004);
• Induce changes in vascular parameters (acute phase response) and ECG (parasympathic stimulation) in rats following on-road exposure to highway PM (Elder et al., 2004), the latter assessed using a custom software program designed by our Cardiac Facility Core for rat ECG analyses (Couderc et al., 2002).
• Induce changes in cardiac function represented by HRV, repolarization parameters (e.g. QT-time, T-wave amplitude and T-wave complexity) and supraventricular and ventricular ectopic beats in patients with coronary heart disease as well as changes in HRV in patients with COPD (preliminary results);
• Can be measured with an Aerosol Time-of-Flight Mass Spectrometer (ATOFMS) down to particle sizes of 10 nm. These improvements permit much better characterization of the ambient aerosol as well as parti- cles in controlled exposure systems (Su et al., 2004).
Inhaled carbon ultrafine particles:
• Have a high deposition efficiency in the respiratory tract, which
is further increased in asthmatics and dur- ing exercise (Chalupa et al.,
2004; Daigle et al., 2003);
• Translocate to extrapulmonary organs via the blood circulation,
dependent on particle chemistry (Oberdör- ster et al., 2002; Kreyling
et al., 2002), and to the central nervous system, via olfactory neurons
(Oberdör- ster et al., 2004);
• Cause changes in adhesion molecule expression of peripheral blood
leukocytes, indicative of systemic ef- fects in healthy and asthmatic
humans (Frampton et al., 2003);
• Alter ischemia-induced hyperemic blood flow in healthy subjects,
indicative of particle effects on endothe- lial function (Pietropaoli,
et al. 2004);
• Decrease the pulmonary diffusing capacity for carbon monoxide
in healthy humans (Pietrapaoli et al., 2004);
• Induce greater oxidative stress in lungs of aged rats compared
to adolescent rats and that ozone co- exposure can increase this response
(Elder et al., 2000);
• Accelerate venous thrombus formation in rats (Silva et al., 2004);
and that the greater sensitivity to UFP induced oxidative stress in the
aged organism is also evident in in vitro primary cell cultures (Finkelstein
et al., 2002).
Our studies show that ambient PM can have significant oxidative capacity, that UFP can induce significant effects not only in the respiratory tract but more importantly affect the vascular and cardiac system and that age and underlying disease (susceptibility factors) are critical modifying factors. Furthermore, our demonstration of their efficient translocation from deposition sites in the respiratory tract to other organs such as heart and CNS provides plausible hypotheses for UFP-induced oxidative stress in those organs. This could be particularly detrimental in susceptible individuals with dysfunctional vascular endothelium as the earliest manifestation of atherosclerotic vascular disease, such as seen in type 2 diabetes. These hypotheses will be tested in our future studies evaluating ambient ultrafine and fine PM responses in diabetics in epidemiological, and clinical studies, performing acute and chronic exposures to ambient ultrafine/fine PM in a diabetic rat model, and in vitro studies to identify mechanisms. The scope of our multidisciplinary studies ranges from detailed characterization of ambient UF/fine PM from different sources to the molecular basis of injury to cells, animals, individuals and populations.