Significance of dermatologic findings in a cohort of depleted uranium-exposed veterans of Iraqi conflicts.

BACKGROUND: Depleted uranium (DU)-containing weapons have been used in military operations since 1991. There is interest in following veterans who were occupationally exposed to DU by either inhalation or retention of fragments. A cohort of DU-exposed Gulf War I veterans has been followed longitudinally at the Baltimore Veterans Administration Medical Center since 1993. OBJECTIVE: The aim was to monitor chronic dermatological findings associated with occupational DU exposure in the 2013 cohort. METHODS: Thirty-five veterans were evaluated. This study was reviewed and approved by the institutional review board and the Baltimore Veterans Administration Medical Center research service. Depleted uranium exposure was measured using creatinine-adjusted urine uranium concentrations (micrograms of uranium per gram of creatinine [µgU/gCrea]). Detailed medical histories, physical examinations, and exposure histories were performed. RESULTS: Using a cutoff level of 0.1 µgU/gCrea, 11 veterans were placed in the high-uranium exposure group, whereas 23 veterans were placed in the low-uranium exposure group. Retained fragments were documented in 91% of the high-exposure group versus that in 13% of the low-exposure group (P < 0.001), and fragment-related scarring was significantly increased in the high-exposure group (P = 0.002). Other dermatological findings such as dermatitis were also assessed. CONCLUSIONS: Fragment retainment and related scarring was significantly increased in veterans exposed to high levels of DU. Continuous monitoring of this cohort will yield interesting dermatological findings related to DU exposure.

Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

A total of 70 military Veterans have been monitored for HPRT T-cell mutations in five separate studies at 2-year intervals over an 8-year period. Systemic depleted uranium (DU) levels were measured at the time of each study by determining urinary uranium (uU) excretion. Each HPRT study included 30-40 Veterans, several with retained DU-containing shrapnel. Forty-nine Veterans were evaluated in multiple studies, including 14 who were in all five studies. This permitted a characterization of the HPRT mutation assay over time to assess the effects of age, smoking and non-selected cloning efficiencies, as well as the inter- and intra-individual variability across time points. Molecular analyses identified the HPRT mutation and T-cell receptor (TCR) gene rearrangement in 1,377 mutant isolates. An unexpected finding was that in vivo clones of HPRT mutant T-cells were present in some Veterans, and could persist over several years of the study. The calculated HPRT mutant frequencies (MFs) were repeatedly elevated in replicate studies in three outlier Veterans with elevated urinary uranium excretion levels. However, these three outlier Veterans also harbored large and persistent in vivo HPRT mutant T-cell clones, each of which was represented by a single founder mutation. Correction for in vivo clonality allowed calculation of HPRT T-cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in HPRT MFs in some Veterans, the results presented here demonstrate that HPRT mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with HPRT mutations and none were found.

Mutagenicity monitoring following battlefield exposures: Molecular analysis of HPRT mutations in Gulf War I veterans exposed to depleted uranium.

Molecular studies that involved cDNA and genomic DNA sequencing as well as multiplex PCR of the HPRT gene were performed to determine the molecular mutational spectrum for 1,377 HPRT mutant isolates obtained from 61 Veterans of the 1991 Gulf War, most of whom were exposed to depleted uranium (DU). Mutant colonies were isolated from one to four times from each Veteran (in 2003, 2005, 2007, and/or 2009). The relative frequencies of the various types of mutations (point mutations, deletions, insertions, etc.) were compared between high versus low DU exposed groups, (based on their urine U concentration levels), with HPRT mutant frequency (as determined in the companion paper) and with a database of historic controls. The mutational spectrum includes all classes of gene mutations with no significant differences observed in Veterans related to their DU exposures.