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Mutagenicity monitoring following battlefield exposures: Longitudinal study of HPRT mutations in gulf war i veterans exposed to depleted uranium
Author(s) -
Albertini Richard J.,
Vacek Pamela M.,
Carter Elizabeth W.,
Nicklas Janice A.,
Squibb Katherine S.,
Gucer Patricia W.,
Engelhardt Susan M.,
McDiarmid Melissa A.
Publication year - 2015
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.21955
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , mutant , in vivo , depleted uranium , mutation , biology , mutation frequency , microbiology and biotechnology , genetics , gene , uranium , materials science , metallurgy
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. Environ. Mol. Mutagen. 56:581–593, 2015. © 2015 Wiley Periodicals, Inc.