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Gail P. Klein,¹ Erin M. Hodge,² Miriam L. Diamond,² Amelia Yip,¹ Tom Dann,³ Gary Stern,⁴ Michael S. Denison,⁵ and Patricia A. Harper^1,6

¹Department of Pharmacology, and ²Department of Geography, Centre for Urban Health Initiatives, University of Toronto, Toronto, Ontario, Canada; ³Analysis and Air Quality Division, Environment Canada, Ottawa, Ontario, Canada; ⁴Freshwater Institute, University of Manitoba, Winnipeg, Manitoba, Canada; ⁵Department of Environmental Toxicology, University of California, Davis, California, USA; ⁶Program in Developmental Biology, Hospital for Sick Children, Toronto, Ontario, Canada

Abstract
Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air ; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR) -based and estrogen receptor (ER) -based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum () of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10-100 times more abundant than that of polychlorinated biphenyls, nitro-polycyclic aromatic hydrocarbons, and organochlorine pesticides, and 10³ to 10⁴ times more abundant than polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways. Key words: AHR, air pollution, CALUX, complex mixtures, endocrine disruption, ER, PAH. Environ Health Perspect 114: 697-703 (2006) . doi:10.1289/ehp.8496 available via http://dx.doi.org/ [Online 29 December 2005]

Address correspondence to P.A. Harper, Program in Developmental Biology, Hospital for Sick Children, 555 University Ave., Toronto, Ontario, Canada M5G 1X8. Telephone: (416) 816-5174. Fax: (416) 813-5252. E-mail: pharper@sickkids.ca

We thank C. Butt (University of Toronto) and F. Wong (Meteorological Service of Canada) .

This research was supported by the Toxic Substances Research Initiative of Health Canada and Environment Canada (M.L.D., T.D., P.A.H, G.S.) , Premier’s Research Excellence Award (M.L.D.) , Canadian Institutes of Health Research (P.A.H.) , U.S. Environmental Protection Agency STAR Grant (RS82867601, M.S.D.) , and the National Institute of Environmental Health Sciences, U.S. National Institutes of Health (ES04699, M.S.D.) .

The authors declare they have no competing financial interests.

Received 13 July 2005 ; accepted 29 December 2005.

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