title: Prevalidation of in vitro continuous flow exposure systems as alternatives to in vivo inhalation safety evaluation experimentations: outcome from MAAPHRI-PCRD5 research program.
abstract: Diesel engine emission aerosol-induced toxicity patterns were compared using both in vitro (organotypic cultures of lung tissue) and in vivo experimentations mimicking the inhalation situation with continuous aerosol flow exposure designs. Using liquid media resuspended diesel particles, we show that toxic response pattern is influenced by the presence of tensioactive agent in the medium which alter particle-borne pollutant bioavailability. Using continuous aerosol exposure in vitro, we show that with high sulfur fuel (300ppm) in the absence of oxidation catalysis, particulate matter was the main toxic component triggering DNA damage and systemic inflammation, while a very limited oxidant stress was evidenced. In contrast, with ultra-low sulfur fuel in the presence of strong diesel oxidation catalysis, the specific role of particulate matter is no longer evidenced and the gas phase then becomes the major component triggering strong oxidant stress, increased NO(2) being the most probable trigger. In vivo, plasma tumor necrosis factor alpha (TNFalpha), lung superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activity levels varied in agreement with in vitro observations. Diesel emission treatment with oxycat provokes a marked systemic oxidant stress. Again NO(2) proved to account for a major part of these impacts. In conclusion, similar anti-oxidant responses were observed in in vitro and in vivo experiments after diesel emission aerosol continuous flow exposures. The lung slice organotypic culture model-exposed complex aerosol appears to be a very valuable alternative to in vivo inhalation toxicology experimentations in rodents.
authors.affiliation: INSERM U644, Université de Rouen, 22 bd Gambetta, 76183 Rouen Cedex, France. jean-paul.morin@univ-rouen.fr
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Morin
authors.forename: Virginie
authors.initials: V
authors.lastname: Hasson
authors.forename: Mamadou
authors.initials: M
authors.lastname: Fall
authors.forename: Eleni
authors.initials: E
authors.lastname: Papaioanou
authors.forename: David
authors.initials: D
authors.lastname: Preterre
authors.forename: Frantz
authors.initials: F
authors.lastname: Gouriou
authors.forename: Veronika
authors.initials: V
authors.lastname: Keravec
authors.forename: Athanasios
authors.initials: A
authors.lastname: Konstandopoulos
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dionnet
mesh_terms: D000280:Administration, Inhalation; D000393:Air Pollutants / Q000633:toxicity*; D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D009569:Nitric Oxide / Q000633:toxicity; D009924:Organ Culture Techniques / Q000379:methods*; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D018675:Toxicity Tests / Q000379:methods*; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D001335:Vehicle Emissions; D009569:Nitric Oxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase