Exposure to ambient particulate matter (PM) is associated with respiratory and cardiovascular disease and lung cancer. In this study, we used size fractionated PM samples (3-7, 1.5-3, 0.95-1.5, 0.5-0.95, and <0.5 microm), collected at four contrasting locations (three urban sites, one remote background) in the UK with a Sierra-Andersen high volume cascade impactor. The H(2)O(2)-dependent oxidant generating capacity of the samples was determined by electron spin resonance with 5,5-dimethyl-1-pyrroline-N-oxide spin trapping. In A549 human lung epithelial cells, we determined the cytotoxicity of samples by LDH assay, and interleukin-8 (IL-8) release as an indicator of their inflammatory potency. Oxidative DNA damage was measured by the formamido-pyrimidine-glycosylase (fpg)-modified comet assay. Marked contrasts were observed for all endpoints. Remote background PM showed the lowest oxidant potential, was neither cytotoxic nor genotoxic and did not increase IL-8 release. For the other samples, effects were found to depend more on sampling location than on size fraction. PM collected at high-traffic locations generally showed the strongest oxidant capacity and toxicity. Significant correlations were observed between the oxidant generating potential and all toxicological endpoints investigated, which demonstrates that measurement of the oxidant generating potential by ESR represents a sensitive method to estimate the toxic potential of PM.

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The chitin portion of the peritrophic matrix in the midgut of the tobacco hornworm, Manduca sexta, is produced by chitin synthase 2 (CHS2), a transmembrane family II glycosyltransferase, located at the apical tips of brush border microvilli. To look for proteins that potentially interact with CHS2, we performed yeast twohybrid screening, identifying a novel chymotrypsin-like protease (CTLP1) that binds to the extracellular carboxyterminal domain of CHS2. The occurrence of this interaction in vivo is supported by co-localization and coimmunoprecipitation data. Based on our findings we propose that chitin synthesis is controlled by an intestinal proteolytic signalling cascade linking chitin synthase activity to the nutritional state of the larvae.

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We have investigated whether short-term nose-only inhalation exposure to electric spark discharge-generated carbon nanoparticles (∼60 nm) causes oxidative stress and DNA damage responses in the lungs of rats (152 μg/m(3); 4 h) and mice (142 μg/m(3); 4 h, or three times 4 h). In both species, no pulmonary inflammation and toxicity were detected by bronchoalveolar lavage or mRNA expression analyses. Oxidative DNA damage (measured by fpg-comet assay), was also not increased in mouse whole lung tissue or isolated lung epithelial cells from rat. In addition, the mRNA expressions of the DNA base excision repair genes OGG1, DNA Polβ and XRCC1 were not altered. However, in the lung epithelial cells isolated from the nanoparticle-exposed rats a small but significant increase in APE-1 mRNA expression was measured. Thus, short-term inhalation of carbon nanoparticles under the applied exposure regimen, does not cause oxidative stress and DNA damage in the lungs of healthy mice and rats.

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