Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in gulf war i veterans exposed to depleted uranium. (13th May 2015)

• Record Type: Journal Article
• Authors: Albertini, Richard J.; Vacek, Pamela M.; Carter, Elizabeth W.; Nicklas, Janice A.; Squibb, Katherine S.; Gucer, Patricia W.; Engelhardt, Susan M.; McDiarmid, Melissa A.
• Is Part Of: Environmental and molecular mutagenesis. Volume 56:Number 7(2015:Aug.)
• Page Start: 581
• Page End: 593
• Publication Date: 2015-05-13
• Subjects: Mutagenesis -- Periodicals; Molecular genetics -- Periodicals; Mutagenèse -- Périodiques; Mutagenèse chimique -- Périodiques; Mutation -- Périodiques; Maladies de l'environnement -- Périodiques; Génétique moléculaire -- Périodiques; 576.542
• DOI: 10.1002/em.21955
• Languages: English
• ISSNs: 0893-6692

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>A total of 70 military Veterans have been monitored for <italic>HPRT</italic> 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 <italic>HPRT</italic> 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 <italic>HPRT</italic> 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 <italic>HPRT</italic> mutation and T‐cell receptor (TCR) gene rearrangement in 1, 377 mutant isolates. An unexpected finding was that <italic>in vivo</italic> clones of <italic>HPRT</italic> mutant T‐cells were present in some Veterans, and could persist over several years of the study. The calculated <italic>HPRT</italic> 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 <italic>in vivo HPRT</italic> mutant T‐cell clones, each of which was represented by a single founder mutation. Correction for <italic>in vivo</italic> clonality allowed calculation of <italic>HPRT</italic> T‐cell mutation frequencies (MutFs). Despite earlier reports of DU associated increases in <italic>HPRT</italic> MFs in some Veterans, the results presented here demonstrate that <italic>HPRT</italic> mutations are not increased by systemic DU exposure. Additional battlefield exposures were also evaluated for associations with <italic>HPRT</italic> mutations and none were found. Environ. Mol. Mutagen. 56:581–593, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>