Effects of Arsenic Compounds on Proliferation and Nitric Oxide Synthesis in C3H 10T 1/2 Murine Fibroblasts

✍ Scribed by Robert V. Cooney; Patrica J. Harwood

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 188 KB
• Volume: 11
• Category: Article
• ISSN: 0268-2605
• DOI: 10.1002/(sici)1099-0739(199705)11:5<397::aid-aoc594>3.0.co;2-t

✦ Synopsis

Exposure to arsenic, either through chronic consumption of contaminated water or inhalation, is associated with increased risk of cancer, yet the mechanism by which arsenicals promote neoplastic change remains undefined. The carcinogenic process involves the formation of heritable genetic changes in the DNA of normal cells and this process may be enhanced by environmental agents that increase cellular proliferation, increase DNA damage and decrease the ability to repair damage or cause immunosuppression. We describe the inhibition of cellular proliferation of C3H 10T1/2 murine fibroblasts in the presence of 1.0 M arsenate or arsenite; yet cacodylic acid had no significant effect on cell growth in culture at this concentration. Both arsenate and cacodylate, at micromolar concentrations, slightly stimulated cell growth and cell density when cells were treated with interferon-␥/lipopolysaccharide (IFN-␥/ LPS). At 1 M, arsenate and cacodylate also slightly increased IFN-␥/LPS-induced nitric oxide (NO) synthesis in this cell line, consistent with the increase in cell number observed, whereas 1 M arsenite significantly increased NO production on a per-cell basis. In contrast, arsenite significantly inhibited NO synthesis at concentrations above 10 M arsenite as, to a lesser extent, did arsenate and cacodylate. These results suggest that ingestion of arsenicals could alter cellular generation of NO and interfere with its associated physiological functions.