John F. Kalinich *, Narayani Ramakrishnan 1, Vilmar Villa, David E. McClain
Depleted uranium/uranyl chloride induces apoptosis in mouse
J774 macrophages
in: Toxicology 179 (2002) 105/114
http://www.worldcat.org/oclc/39231761http://www.laka.org/docu/boeken/pdf/6-05-0-00-30.pdf page 2
Applied Cellular Radiobiology Department, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD
20889-5603, USA
(
http://www.usuhs.edu/afrri/ , Denglisch)
"Abstract
Depleted uranium entering the body as a result of inhalation or embedded fragments becomes associated to a great extent with macrophages. As part of our continuing studies on the health effects of internalized depleted uranium, we investigated the effect of soluble depleted uranium/uranyl chloride on the mouse macrophage cell line, J774. Using a cytochemical staining protocol specific for uranium, we found that uranium uptake by the macrophages increased in a time-dependent manner. Treatment with 1, 10, or 100 mM depleted uranium/uranyl chloride resulted in decreased viability of the J774 cells within 24 h. Flow cytometric analysis of the treated cells with annexin V showed the translocation of phosphatidylserine from the inner face of the plasma membrane to the outer surface indicating the loss of phospholipid symmetry and the beginning of the apoptotic process. Significant differences in annexin V labeling between control cells and cells treated with 100 mM depleted uranium/uranyl chloride were apparent within 2 h. Other events associated with apoptosis, including morphological changes and DNA fragmentation, were also apparent after depleted uranium/uranyl chloride treatment. These results suggest that the uptake and concentration of soluble depleted uranium by macrophages initiates events that results in the apoptotic death of these cells. c 2002 Elsevier Science Ireland Ltd. All rights reserved."
http://www.laka.org/docu/boeken/pdf/6-05-0-00-30.pdf page 2
"Military Medicine 2002 Feb;167(2 Suppl):117-9.
(
http://www.worldcat.org/oclc/55948875 , Denglisch)
Health effects of embedded depleted uranium.
McClain DE1, Benson KA, Dalton TK, Ejnik J, Emond CA, Hodge SJ, Kalinich JF, Landauer MR, Livengood DR, Miller AC, Pellmar TC, Stewart MD, Villa V, Xu J.
Author information
1Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Bethesda, MD 20889-5603, USA.
(
http://www.usuhs.edu/afrri/ , Denglisch)
Abstract
The health effects of embedded fragments of depleted uranium (DU) are being investigated to determine whether current surgical fragment-removal policies are appropriate for this metal. The authors studied rodents implanted with DU pellets as well as cultured human cells exposed to DU compounds. Results indicate that uranium from implanted DU fragments distributes to tissues distant from implantation sites, including bone, kidney, muscle, and liver. Despite levels of uranium in kidney that would be nephrotoxic after acute exposure, no histological or functional kidney toxicity was observed with embedded DU, indicating that the kidney adapts when exposed chronically. Nonetheless, further studies of the long-term health impact are needed. DU is mutagenic and transforms human osteoblastic cells into a tumorigenic phenotype. It alters neurophysiological parameters in rat hippocampus, crosses the placental barrier, and enters fetal tissue. Preliminary data also indicate decreased rodent litter size when animals are bred 6 months or longer after DU implantation.
PMID: 11873491 [PubMed - indexed for MEDLINE]"
https://www.ncbi.nlm.nih.gov/pubmed/11873491"Reviews on environmental health 2007 Jan-Mar;22(1):75-89.
( https://www.ncbi.nlm.nih.gov/nlmcatalog?term="Rev+Environ+Health"%5Bta%5D , Denglisch)
(
http://www.worldcat.org/oclc/726831606 , Denglisch)
A review of depleted uranium biological effects: in vitro and in vivo studies.
Miller AC1, McClain D.
Author information
1Uniformed Services University of the Health Sciences, Armed Forces Radiobiology Research Institute, 8901 Wisconsin Avenue, Building 42, Bethesda, MD 20889-5603, USA. millera@afrri.usuhs.mil
(
http://www.usuhs.edu/afrri/ , Denglisch)
Abstract
The use of depleted uranium in armor-penetrating munitions remains a source of controversy because of the numerous unanswered questions about its long-term health effects. Although no conclusive epidemiologic data have correlated DU exposure to specific health effects, studies using cultured cells and laboratory rodents continue to suggest the possibility of leukemogenic, genetic, reproductive, and neurological effects from chronic exposure. Until issues of concern are resolved with further research, the use of depleted uranium by the military will continue to be controversial.
PMID: 17508699 [PubMed - indexed for MEDLINE]"
https://www.ncbi.nlm.nih.gov/pubmed/17508699http://www.degruyter.com/dg/viewarticle/j$002freveh.2007.22.1$002freveh.2007.22.1.75$002freveh.2007.22.1.75.xml;jsessionid=C9F0CEA87CD33C59F8136333AE224F04
"Abstract
Journal of environmental radioactivity 2003;64(2-3):247-59.
(
http://www.journals.elsevier.com/journal-of-environmental-radioactivity/ , Denglisch)
(
http://www.worldcat.org/oclc/38993733 , Denglisch)
Genomic instability in human osteoblast cells after exposure to depleted uranium: delayed lethality and micronuclei formation.
Miller AC1, Brooks K, Stewart M, Anderson B, Shi L, McClain D, Page N.
Author information
1Applied Cellular Radiobiology Department Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA.
(
http://www.usuhs.edu/afrri/ , Denglisch)
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 instability, 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 lethality 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 endpoints, 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 been exposed to nontoxic concentrations of DU. While clones isolated from gamma-irradiated cells (at doses equitoxic to metal exposure) generally demonstrated an increase in micronuclei, most clonal progeny of Ni-exposed cells did not. These studies demonstrate that DU exposure in vitro results in genomic instability manifested as delayed reproductive death and micronuclei formation.
PMID: 12500809 [PubMed - indexed for MEDLINE]"
https://www.ncbi.nlm.nih.gov/pubmed/12500809
