1. Comparison of the Biological Effects of Sudbury Particulate Matter (SPaM) with Other Particulate Types: Acute and Chronic Studies Sarah M. White Stacey Ritz, PhD.

2. Health Effects of Air Pollution Mortality estimates: 6 000 annually in Ontario (OMA) 21 000 annually in Canada (CMA) Compare to breast cancer (5 300), prostate cancer (4 300), influenza & pneumonia (8 000), lung cancer (20 000) (StatsCan & Canadian Cancer Society) 500 000 annually worldwide (WHO)

3.  Asthma exacerbations  Trigger for cardiovascular events in those with pre-existing disease  Exposure may facilitate the development of other disorders  Allergy  Atherosclerosis  Autoimmunity (?) Health Effects of Air Pollution

4. Mechanisms of Health Effects  Oxidative stress:  reactive organic compounds and transition metals involved in production of reactive oxygen species (ROS)  Inflammation:  Release of cytokines by airway epithelial cells and alveolar macrophages

6. Particulate Matter (PM)  The PM component of air pollution is known to have adverse health effects  Smaller particles are more toxic  Experimental models of PM:  Diesel exhaust particles (DEPs): from a diesel engine, standardized  Ambient particles: collected from ambient air, reflects local environment

7. DEP (Diesel exhaust Particles)  carbon core with organic compounds  polyaromatic hydrocarbons (PAH), quinones, aldehydes, nitroaromatic hydrocarbons and heterocyclics.  DEP makes up a significantly large portion of PM  Depends on local contributors to PM  Mostly fine and ultrafine in size  Standardized DEP is widely used in experimental settings (cell culture, animal studies, human studies) Transmission electron microscopy image of DEP http://www.transportation.anl.gov /engines/diesel_structure.html

8. EHC-93  Ambient urban sample from Ottawa ON  Bronchial epithelial cells exposed to EHC-93 upregulate expression of inflammatory cytokines  GM-CSF, IL-8 and IL-1 (Fujii et al, 2001)  Used in numerous cell culture and animal models

9. Sudbury Particulate Matter (SPaM)  Collected by Kati McCartney of the Ritz lab in 2006  Reflects local environment in Sudbury, which is impacted by local industrial activities Image of the particulate collected from one filter (McCartney, 2009)

10. Transition Metal Content of PM Samples (McCartney,2009)

11. Hypothesis Ambient PM samples will elicit greater inflammatory effects than DEPs Transition metal content Tested in 3 experimental settings: Cell cultures (bronchial epithelial cells) Acute exposure in mice Chronic exposure in mice

12. Cell Culture: ALI  Previous work by McCartney et al indicated that exposure to SPaM elicited enhanced pro-inflammatory cytokine production (IL-8) in cells grown under standard conditions  BEAS2B cells were grown in ALI (Air Liquid Interface) cell culture to better model in vivo. http://www.mattek.com/pages/in_vitro_basics/ali-schematic-600.gif

13. IL-8 production by airway epithelial cells after PM exposure (ANOVA on Ranks P=0.017)

14. Acute Study  Balb/c mice exposed to 250ug of PM via intranasal instillation  Background exposure to PM reduced by specialized caging system  Mice euthanized at 12h post- exposure  Airway inflammation  Acute phase response

15. Airway Neutrophilia after acute exposure to PM (ANOVA P=0.006)

16. Control

17. DEP

18. EHC-93

19. SPaM

20. Chronic Study  Balb/c mice exposed to aerosolized suspensions of PM in chambers  15 min a day, five days a week  Concentration of aerosol in chamber is 400ug/m 3  estimated dose of 24 ug/kg/week  Comparable to ambient exposure in typical urban area

21. Neutrophilic Airway Inflammation During Chronic Exposure

26. Implications  The acute study reinforces the need for occupational health and safety for workers who can be exposed to large doses of PM.  There was signs of inflammation in all PM treated groups  The chronic study shows some evidence of physiological changes in the respiratory epithelium

27. Acknowledgements  Special thanks to all the members of Team Ritz:  Kati McCartney, Cathy Brummer, Jane Bulloch, Nya Fraleigh, Sandhya Khurana PhD.  Especially Stacey Ritz PhD.  To all the NOSM Research lab members especially Joe Eibl and Heather Peltch for their support.

28. Questions