Observation of radiation-specific damage in cells exposed to depleted uranium: hprt gene mutation frequency

Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Published data from our laboratory have demonstrated that DU exposure in vitro to immortalized human osteoblast cells (HOS) is both neoplastically transforming and genotoxic. Recent animal studies have also shown that DU is leukemogenic and genotoxic. DU possesses both a radiological (alpha particle) and chemical (metal) component. Since DU has a low specific activity in comparison to natural uranium, it is not considered to be a significant radiological hazard. The potential contribution of radiation to DU-induced biological effects is unknown, and the involvement of radiation in DU-induced biological effects could have significant implications for current risk estimates for internalized DU exposure. The purpose of the current study was to measure the induction of mutagenic damage in V79 cells and to determine if radiation plays a role in the induction of that damage. Mutagenicity at the hypoxanthine (guanine) phosphoribosyltransferase (hprt) locus was measured by selection with 6-thioguanine. There was a dose-dependent increase in mutagenic response following DU exposure (10-50μm); the average increase in mutagenicity above background ranged from 2.54±1.19 to 8.75±1.8(P<0.05). Using the same concentration (25μM) of two uranyl nitrate compounds that have different uranium isotopic concentrations and, therefore, different specific activities, we examined the effect on hprt mutant frequency in vitro. V79 cells were exposed to either 238U-uranyl nitrate, specific activity 0.33μCi/g, or DU-uranyl nitrate, specific activity 0.44μCi/g, delivered at a concentration of 25μM for 24 h. Results showed, that at equal uranium concentration, a 1.33-fold increase in specific activity resulted in a 1.27±0.11-fold (P<0.05) increase in hprt mutant frequency. Taken together these data support earlier results showing that radiation can play a role in DU-induced biological effects in vitro