title: Measures of genotoxicity in Gulf war I veterans exposed to depleted uranium.
abstract: Exposure to depleted uranium (DU), an alpha-emitting heavy metal, has prompted the inclusion of markers of genotoxicity in the long-term medical surveillance of a cohort of DU-exposed Gulf War veterans followed since 1994. Using urine U (uU) concentration as the measure of U body burden, the cohort has been stratified into low-u (<0.10 μg U/g creatinine) and high-u groups (≥ 0.10 μg U/g creatinine). Surveillance outcomes for this cohort have historically included markers of mutagenicity and clastogenicity, with past results showing generally nonsignificant differences between low- vs. high-U groups. However, mean hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutant frequencies (MFs) have been almost 50% higher in the high-U group. We report here results of a more comprehensive protocol performed in a 2009 evaluation of a subgroup (N = 35) of this cohort. Four biomarkers of genotoxicity [micronuclei (MN), chromosome aberrations, and MFs of HPRT and PIGA] were examined. There were no statistically significant differences in any outcome measure when results were compared between the low- vs. high-U groups. However, modeling of the HPRT MF results suggests a possible threshold effect for MFs occurring in the highest U exposed cohort members. Mutational spectral analysis of HPRT mutations is underway to clarify a potential clonal vs. a threshold uU effect to explain this observation. This study provides a comprehensive evaluation of a human population chronically exposed to DU and demonstrates a relatively weak genotoxic effect of the DU exposure. These results may explain the lack of clear epidemiologic evidence for U carcinogenicity in humans. Environ. Mol. Mutagen., 2011. © 2011 Wiley-Liss, Inc.
authors: Occupational Health Program, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
authors: Melissa A
authors: MA
authors: McDiarmid
authors: Richard J
authors: RJ
authors: Albertini
authors: James D
authors: JD
authors: Tucker
authors: Pamela M
authors: PM
authors: Vacek
authors: Elizabeth W
authors: EW
authors: Carter
authors: Marina V
authors: MV
authors: Bakhmutsky
authors: Marc S
authors: MS
authors: Oliver
authors: Susan M
authors: SM
authors: Engelhardt
authors: Katherine S
authors: KS
authors: Squibb
mesh_terms: D000328:Adult; D004781:Environmental Exposure; D047830:Gulf War; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000187:drug effects; D014501:Uranium / Q000633:toxicity* / Q000652:urine; D014728:Veterans
chemical_list: D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein; D014501:Uranium; D007041:Hypoxanthine Phosphoribosyltransferase