Silica-induced apoptosis in vitro and in vivo

Toxicol Lett. 1999 Sep 5;108(2-3):335-9. doi: 10.1016/s0378-4274(99)00107-1.

Abstract

Silica exposure results in an initially acute inflammatory response followed by chronic fibrotic change. The mechanism for the maintenance of silica-induced inflammation has not been understood yet. In silica-induced acute inflammation and chronic fibrosis, various mediators such as reactive oxygen species, cytokines and growth factors are released. And these substances are suggested to have the regulatory role for the inflammation and fibrosis by possessing the potential to influence apoptosis. To demonstrate the apoptosis as an underlying mechanism for the development of silicosis, in vitro and in vivo models were designed. In in vitro study, we evaluated that apoptotic cell fraction in silica (10, 50 microg/cm2)-treated A549 cells was significantly increased in comparison with control by FACS (fluorescein activated cell sorter). Also genomic DNA from silica (10, 50 microg/cm2)-treated A549 showed DNA ladder formation while control and 1 microg/cm2 groups didn't. In in vivo study, total cell numbers and apoptotic cell numbers of BAL (bronchoalveolar lavage) fluid from silica (10, 20, 40 mg/kg)-instilled rats were significantly higher than control group from 1 week. From these results, we concluded acute and chronic presence of apoptosis may contributes to silica-induced acute inflammation and chronic fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Bronchoalveolar Lavage Fluid / cytology
  • Cell Count
  • Cell Survival
  • DNA Damage
  • Dose-Response Relationship, Drug
  • Flow Cytometry
  • Humans
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / toxicity*
  • Silicosis / etiology
  • Tumor Cells, Cultured

Substances

  • Silicon Dioxide