title: Biphasic culture of rat lung slices for pharmacotoxicological evaluation of complex atmospheres.
abstract: The relevance to the in vivo situation of in vitro toxicity studies of complex atmospheres has frequently been limited by the procedures used for the exposure of the biological samples. We have evaluated from on-road measurements the size distribution pattern and the subsequent respiratory tract deposition rates of particulate matter from urban atmospheric aerosols, which are in the range of 110 and 3 pg/cm2 per min for tracheobronchial and alveolar areas, respectively. Continuous flow-through rotating chambers and a specific design for exhaust sampling and dilution with controlled adjustment of pO2 and pCO2 to 20% and 5%, respectively, have been developed to expose biphasic air/liquid organotypic cultures of rat lung slices to continuous flows of diluted exhausts from diesel engines with preservation of the physicochemical properties of the exhaust. The size distribution of the particulate matter and the bioavailability of pollutants were preserved, thus allowing us to closely mimic in vitro the in vivo atmosphere/tissue interactions that occur mainly through diffusion mechanisms. The toxicity response profile has been assessed in terms of tissue viability, oxidative stress, DNA injury, and the early phase of inflammatory reaction. Exhaust filtration, addition to fuel of rapeseed methyl ester, and preincubation of lung tissue with soy isoflavones modulated the toxicity response profile of exhausts. The importance of preserving both particulate matter size distribution and adsorbed pollutant bioavailability, which could not be ascertained using more classical in vitro approaches, is discussed and should be considered a prerequisite for further developments of in vitro studies to modelize in vivo inhalation of complex atmospheres.
authors.affiliation: INSERM E9920, Faculté de Médecine Pharmacie, Université de Rouen, France.
authors.forename: A
authors.initials: A
authors.lastname: Bion
authors.forename: M
authors.initials: M
authors.lastname: Fal
authors.forename: F
authors.initials: F
authors.lastname: Gouriou
authors.forename: E
authors.initials: E
authors.lastname: Le Prieur
authors.forename: F
authors.initials: F
authors.lastname: Dionnet
authors.forename: J P
authors.initials: JP
authors.lastname: Morin
mesh_terms: D000336:Aerosols; D000393:Air Pollutants / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D004249:DNA Damage; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009924:Organ Culture Techniques / Q000295:instrumentation / Q000379:methods; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D000336:Aerosols; D000393:Air Pollutants; D001335:Vehicle Emissions