Publication Laka-library:
Genomic instability in human osteoblast cells after exposure to depleted uranium

AuthorMiller, Brooks
6-05-0-00-31.pdf
DateFebruary 2002
Classification 6.05.0.00/31 (DEPLETED URANIUM - GENERAL (F.I. HEALTH CONSEQUENCES))
Front

From the publication:

                    Journal of Environmental Radioactivity 64 (2003) 247–259
                                                                      www.elsevier.com/locate/jenvrad




    Genomic instability in human osteoblast cells
    after exposure to depleted uranium: delayed
         lethality and micronuclei formation
      Alexandra C. Miller a,∗, Kia Brooks a, Michael Stewart a,
    Blake Anderson a, Lin Shi b, David McClain a, Natalie Page b
a
    Applied Cellular Radiobiology Department Armed Forces Radiobiology Research Institute, Bethesda,
                                          MD 20889-5603 USA
     b
       Molecular Oncology Branch, Division of Cancer Treatment, National Cancer Institute, National
                               Institute Health, Bethesda, MD 20892 USA
                          Received 30 June 2001; accepted 27 February 2002

Abstract
   It is known that radiation can induce a transmissible persistent destabilization of the genome.
We have established an in vitro cellular model using HOS cells to investigate whether genomic
instability plays a role in depleted uranium (DU)-induced effects. Transmissible genomic insta-
bility, manifested in the progeny of cells exposed to ionizing radiation, has been characterized
by de novo chromosomal aberrations, gene mutations, and an enhanced death rate. Cell lethal-
ity and micronuclei formation were measured at various times after exposure to DU, Ni, or
gamma radiation. Following a prompt, concentration-dependent acute response for both end-
points, there was de novo genomic instability in progeny cells. Delayed reproductive death
was observed for many generations (36 days, 30 population doublings) following exposure to
DU, Ni, or gamma radiation. While DU stimulated delayed production of micronuclei up to
36 days after exposure, levels in cells exposed to gamma-radiation or Ni returned to normal
after 12 days. There was also a persistent increase in micronuclei in all clones isolated from
cells that had bee