Radiation Measurements 42 (2007) 1029 – 1032

Radiation Measurements 42 (2007) 1029 – 1032
Observation of radiation-specific damage in cells exposed to depleted
uranium: hprt gene mutation frequency
Alexandra C. Millera,∗, Michael Stewarta, Rafael Rivasa, Steve Marinob,
Gerhard Randers-Pehrsonb, Lin Shia
aScience Research Departments, Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences,
8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA
bCenter for Radiological Research, Columbia University, 630 W. 168th St. VC11-215, New York, NY 10032, USA
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 (10.50 m); 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 (25 M) 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 0.33 Ci/g, or DU-uranyl nitrate, specific activity 0.44 Ci/g, delivered at
a concentration of 25 M 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.

…..Although the data indicate that radiation is involved in DU
effects in vitro, several questions remain unanswered. We neither
know the extent to which radiation contributes to the effects
exerted by DU nor understand its mechanism(s). Furthermore,
we can only speculate as to whether the radiation and chemical
effects are synergistic. Limited studies have shown that a
nonradioactive metal like cadmium combined with gamma radiation
can result in a synergistic response in vivo (Prise et al.,
1998). It is intriguing to ask whether radiation actually plays
a significant role in DU cellular effects perhaps through nontargeted
effects of radiation exposure. Several recent radiation
studies have demonstrated the important role that bystander effects
have in cellular radiation response by causing damage in
unirradiated neighboring cells (Prise et al., 1998; Zhou et al.,
2000; Belyakov et al., 2001; Sawant et al., 2001). In the case
of DU, cells not traversed by an alpha particle may be vulnerable
to radiation-induced effects as well as chemically induced
While the data presented here do not fully and definitively
answer the question as to the contribution of radiation-induced
damage in DU cellular effects, they do provide additional
evidence of radiation involvement in the cellular effects of
DU and, therefore, potentially in DU-associated health effects.
Considering that conventional understanding of potential DU
health effects assumes that chemical effects are of greatest concern,
these results could have a significant impact on DU risk

One Response to “”

  1. CaptD Says:

    More good data on the Bad effects of DU…
    Liked and Tweeted…

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