Effects of simulated pulmonary surfactant on the cytotoxicity and DNA-damaging activity of respirable quartz and kaolin.
Respirable-sized quartz and kaolin dusts were pretreated with simulated pulmonary surfactant dispersions of dipalmitoyl phosphatidylcholine (DPPC) in saline to model the conditioning of particles depositing in alveolar regions of the lung. DPPC-treated and untreated dusts were used to challenge lavaged rat pulmonary alveolar macrophages in vitro. Cytotoxicity was determined over a 5-d period using both total and viable cell counts from a fluorescence-based viability assay. DNA damage, as an indication of genotoxicity, was determined over a 7-d period by the single-cell gel electrophoresis assay. Untreated quartz and kaolin both expressed a significant and potent cytotoxicity, which increased with concentration and time. DPPC-surfactant pretreatment delayed significant expression of this cytotoxicity until 3 to 5 d after challenge. Untreated quartz also caused DNA damage, which increased with concentration and time. DPPC-surfactant treatment of quartz delayed most DNA damage expression to 5 and 7 d. Untreated kaolin expressed weaker activity for DNA damage, significant at the highest concentration through 5 d, and at the higher concentrations on d 7. Surfactant treatment delayed most kaolin activity for DNA damage to 7 d after challenge.
Gao
N
N
Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505, USA.
Keane
M J
MJ
Ong
T
T
Wallace
W E
WE
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000494:pharmacology; D000818:Animals; D000930:Antidiarrheals / Q000633:toxicity*; D018929:Cell Culture Techniques; D004249:DNA Damage; D004391:Dust; D019570:Inhalation Exposure; D007616:Kaolin / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010316:Particle Size; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology; D011663:Pulmonary Surfactants / Q000494:pharmacology*; D011791:Quartz / Q000633:toxicity*; D051381:Rats; D013997:Time Factors
D000930:Antidiarrheals; D004391:Dust; D011663:Pulmonary Surfactants; D011791:Quartz; D007616:Kaolin; D015060:1,2-Dipalmitoylphosphatidylcholine