title: Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt and iron.
abstract: Tungsten-based materials have been proposed as replacements for depleted uranium in armor-penetrating munitions and for lead in small-arms ammunition. A recent report demonstrated that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound. The early genetic changes occurring in response to embedded metal fragments are not known. In this study, we utilized two cultured rodent myoblast cell lines, exposed to soluble tungsten alloys and the individual metals comprising the alloys, to study the genotoxic effects. By profiling cell transcriptomes using microarray, we found slight, yet distinct and unique, gene expression changes in rat myoblast cells after 24 h metal exposure, and several genes were identified that correlate with impending adverse consequences of ongoing exposure to weapons-grade tungsten alloy. These changes were not as apparent in the mouse myoblast cell line. This indicates a potential species difference in the cellular response to tungsten alloy, a hypothesis supported by current findings with in vivo model systems. Studies examining genotoxic-associated gene expression changes in cells from longer exposure times are warranted.
authors.affiliation: Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services, Washington, D.C. 20201, USA. Stephanie.Bardack@hhs.gov.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bardack
authors.affiliation: Department of Anatomy, Physiology, and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. clifton.dalgard@usuhs.edu.
authors.forename: Clifton L
authors.initials: CL
authors.lastname: Dalgard
authors.affiliation: Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Avenue, Bethesda, MD 20889, USA. john.kalinich@usuhs.edu.
authors.forename: John F
authors.initials: JF
authors.lastname: Kalinich
authors.affiliation: Daniel K. Inouye Graduate School of Nursing, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA. christine.kasper@va.gov.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Kasper
mesh_terms: D000818:Animals; D002460:Cell Line; D051379:Mice; D009152:Mutagenicity Tests; D032446:Myoblasts / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D014414:Tungsten / Q000633:toxicity*; D014857:Warfare; D014950:Wounds, Penetrating / Q000150:complications*
chemical_list: D014414:Tungsten