Apoptosis induction in vitro by quartz and kaolin dusts.
Keane-M; Gao-N; Wallace-W
Med Lav 2002 Oct; 93(Suppl):S40
Respirable quartz and kaolin dusts were used to study induction of apoptosis in NR 8383 rat alveolar macrophages in vitro and in vivo by intratracheal instillation in male Sprague- Dawley rats. While quartz is a fibrogenic respirable mineral dust, kaolin, a silicate mineral similar to silica, is not generally considered fibrogenic, but has similar cytotoxic properties in vitro. Both dusts were <5 um fractions. In vitro concentrations ranged from 50-400 ug/ml, and the instilled animals received 4 or 20 mg in 0.5 ml saline. In vitro apoptosis methods included ELISA assays for nucleosomes, terminal deoxynucleotidyl transferase-mediated dUTP-fluorescein nick-end labeling (TUNEL) assays, and DNA ladders for apoptotic fragments. In vivo methods include TUNEL assays for lung tissue and flow cytometry for cells in bronchial alveolar lavage (BAL). In vitro results indicated that quartz induces apoptosis in a dose-dependent and time-dependent manner, while kaolin showed activity only a the highest (400 ug/ml) concentration in the TUNEL assay and slight activity at the 200 and 400 ug/ml points in the EUSA assay. Time course studies in vitro at 100 ug/rnl showed apoptosis at 6h, 12h, and 1,3, and 5 days for quartz, but only at 5 days for kaolin. The effect of serum on the dose-response is discussed. In vivo results show a time-dependent increase of apoptosis in the EUSA assay at both 4 and 20 mg doses, at times ranging from 2 days to 90 days. Kaolin does not show a significant response at any time points for the ELISA. Apoptotic cells as determined using flow cytometry showed a time-and concentration-dependent increase for quartz and no significant response for kaolin at times ranging from 2 to 90 days.
Respiratory-system-disorders; Respiratory-irritants; Respirable-dust; Quartz-dust; In-vitro-study; In-vivo-study; Animal-studies; Laboratory-animals; Cytotoxins
Abstract; Conference/Symposia Proceedings
Work Environment And Workforce: Mixed Exposures; Research Tools and Approaches: Exposure Assessment Methods
La Medicina del Lavoro. 3rd International Symposium on Silica, Silicosis, Cancer and Other Diseases, S. Margherita Ligure, 21-25 October 2002