The role of Fe(II) in dust induced carcinogenesis.
Department of Environmental Medicine, School of Medicine, New York University, Tuxedo, New York 1997 Mar; :1-15
The carcinogenicity of ferrous ion in solution and ferrous containing particles was investigated in Syrian-hamster-embryo (SHE) and human-tracheal-epithelial cells in-vitro. An attempt was made to determine the mechanism of ferrous containing dust induced carcinogenesis and to compare the responsiveness of oxidative stress response transcription factors to ferrous ion treatments. The mechanism of ferrous coated dust induced carcinogenesis was investigated using dichorofluorescein (DCF) and 8-oxo-deoxyguanosine formation. Findings indicated that ferrous ion in aqueous solution is cytotoxic, but not transforming in SHE cells. In contrast, when ferrous ion was deposited on a particle and then phagocytized by these cells, the released ferrous ion gave rise to cellular transformation. These findings suggested that ferrous ions in solution were difficult to incorporate into cells, and when internalized, any free iron would be strongly associated with proteins such as ferritin and transferrin and therefore not be available. Since the redox activity of ferrous ion is pH dependent, a low pH in the stomach can kinetically render the ion inactive. Once a particle containing ferrous ion is inhaled, the ferrous ion will be subsequently converted in the lung to ferric ion, resulting in the formation of reactive oxygen species, which can damage lung cells and cause cytotoxicity.
NIOSH-Grant; Pulmonary-system-disorders; Cancer; Carcinogens; Iron-compounds; Mammalian-cells; In-vitro-studies; Free-radicals
Environmental Medicine New York University Med Center Long Meadow Road Tuxedo, NY 10987
Final Grant Report
NTIS Accession No.
Department of Environmental Medicine, School of Medicine, New York University, Tuxedo, New York
New York University, New York, New York