title: Mercuric chloride damages cellular DNA by a non-apoptotic mechanism.
abstract: Mercury is a xenobiotic metal that is well known to adversely affect the immune system, however, little is known as to the molecular mechanism. Recently, it has been suggested that mercury may induce immune dysfunction by triggering apoptosis in immune cells. Here, we studied the effects of Hg(2+) (HgCl(2)) on U-937 cells, a human cell line with monocytic characteristics. We found that these cells continued to proliferate when exposed to low doses of mercury between 1 and 5 microM. Using the single cell gel electrophoresis (SCGE) or 'comet' assay, we found that mercury damaged DNA at these levels. Between 1 and 50 microM Hg(2+), comet formation was concentration-dependent with the greatest number of comets formed at 5 microM mercury. However, the appearance of mercury-induced comets was qualitatively different from those of control cells treated with anti-fas antibody, suggesting that although mercury might damage DNA, apoptosis was not involved. This was confirmed by the finding that cells treated with 5 microM mercury were negative for annexin-V binding, an independent assay for apoptosis. These data support the notion that DNA damage in surviving cells is a more sensitive indicator of environmental insult than is apoptosis, and suggests that low-concentrations of ionic mercury may be mutagenic.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI 48202, USA.
authors.forename: E Y
authors.initials: EY
authors.lastname: Ben-Ozer
authors.forename: A J
authors.initials: AJ
authors.lastname: Rosenspire
authors.forename: M J
authors.initials: MJ
authors.lastname: McCabe
authors.forename: R G
authors.initials: RG
authors.lastname: Worth
authors.forename: A L
authors.initials: AL
authors.lastname: Kindzelskii
authors.forename: N S
authors.initials: NS
authors.lastname: Warra
authors.forename: H R
authors.initials: HR
authors.lastname: Petty
mesh_terms: D017302:Annexins / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D020552:Comet Assay; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D008627:Mercuric Chloride / Q000633:toxicity*; D009000:Monocytes / Q000187:drug effects
chemical_list: D017302:Annexins; D008627:Mercuric Chloride; D004247:DNA