Genotoxic changes to rodent cells exposed in vitro to tungsten, nickel, cobalt and iron.

Stephanie Bardack,Christine E Kasper,John F Kalinich,Clifton L Dalgard

doi:10.3390/ijerph110302922

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.

Highlights

IntroductionRetained or embedded fragment wounds (shrapnel) have long been a hazard of war
Retained or embedded fragment wounds have long been a hazard of war
Previous research showed that embedded pellets of a military-grade alloy of tungsten/nickel/cobalt induced highly-aggressive metastatic rhabdomyosarcomas in laboratory rats [25], while one composed of tungsten/nickel/iron did not [29]

Summary

Introduction

Retained or embedded fragment wounds (shrapnel) have long been a hazard of war. Modern warfare and its associated technological advances have produced munitions that have increased in both range and lethality. Too have the devices designed to protect the warfighter from the effects of these same munitions. Where previously an injury from exploded ordnances would likely have proved fatal, advances in both protective equipment and medical treatment have rendered even the most severe injuries survivable. That of removing retained or embedded fragments, has changed little over time. Military medical practice has long held that fragments posing no immediate threat to the individual can remain in place. The composition of munitions has changed, and many modern munitions may pose a health hazard via long-term exposure to the retained embedded fragments

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