Toxicity of depleted uranium complexes is independent of p53 activity

Heintze, Ellie; Aguilera, Camille; Davis, Malia; Fricker, Avery; Li, Qiang; Martinez, Jesse D.; Gage, Matthew J.

doi:10.1016/j.jinorgbio.2010.10.010

Cited by 10 publications

(4 citation statements)

References 39 publications

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“…Our results both support previous reports that uranium exposure leads to DNA damage both in vitro and in human populations, and provides a plausible mechanism for those observations through inhibition of DNA repair proteins. UA alone displayed limited cytotoxicity at levels below 10 μM in keeping with other reports in the literature where cytotoxicity is detected at uranium levels at or greater than 100 μM (Stearns et al, 2005; Periyakaruppan et al, 2007; Thiebault et al, 2007; Milgram et al, 2008; Rouas et al, 2010; Heintze et al, 2011; Orona and Tasat, 2012; Garmash et al, 2014). However, there is evidence that elevated blood uranium levels are associated with increased DNA damage (Popp et al, 2000; Guimaraes et al, 2010; Lourenco et al, 2013) and decreased DNA repair capacity in human populations (Au et al, 1995; Au et al, 1998; Au et al, 2010).…”

Section: Discussionsupporting

confidence: 89%

“…Uranium has been reported to be cytotoxic at high concentrations (>100 μM) in a number of cell lines (Stearns et al, 2005; Coryell and Stearns, 2006; Knobel et al, 2006; Periyakaruppan et al, 2007; Thiebault et al, 2007; Milgram et al, 2008; Periyakaruppan et al, 2009; Darolles et al, 2010; Rouas et al, 2010; Heintze et al, 2011; Orona and Tasat, 2012; Garmash et al, 2014), but there is less published information regarding lower concentrations of uranium. We compared uranyl acetate (UA) toxicity in human embryonic kidney cells (HEK293) and normal human keratinocytes (HEKn).…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Cooper

Dashner

Tsosie

et al. 2016

Toxicology and Applied Pharmacology

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Uranium has radiological and non-radiological effects within biological systems and there is increasing evidence for genotoxic and carcinogenic properties attributable to uranium through its heavy metal properties. In this study, we report that low concentrations of uranium (as uranyl acetate; <10 μM) is not cytotoxic to human embryonic kidney cells or normal human keratinocytes; however, uranium exacerbates DNA damage and cytotoxicity induced by hydrogen peroxide, suggesting that uranium may inhibit DNA repair processes. Concentrations of uranyl acetate in the low micromolar range inhibited the zinc finger DNA repair protein poly(ADP-ribose) polymerase (PARP)-1 and caused zinc loss from PARP-1 protein. Uranyl acetate exposure also led to zinc loss from the zinc finger DNA repair proteins Xeroderma Pigmentosum, Complementation Group A (XPA) and aprataxin (APTX). In keeping with the observed inhibition of zinc finger function of DNA repair proteins, exposure to uranyl acetate enhanced retention of induced DNA damage. Co-incubation of uranyl acetate with zinc largely overcame the impact of uranium on PARP-1 activity and DNA damage. These findings present evidence that low concentrations of uranium can inhibit DNA repair through disruption of zinc finger domains of specific target DNA repair proteins. This may provide a mechanistic basis to account for the published observations that uranium exposure is associated with DNA repair deficiency in exposed human populations.

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Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Cooper

Dashner

Tsosie

et al. 2016

Toxicology and Applied Pharmacology

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“…(45) The comprehensive mechanisms by which DU affects the metabolic functions of the human cells remain to be adequately explored, but many researchers have confidently suggested a cellular and molecular toxicity of DU. (46) Ingestion of food or drinking water contaminated by DU or the inhalation of contaminated air and dust are the most critical pathways of exposure to environmental DU for the general public, whereas direct dermal contact is an insignificant pathway because DU cannot permeate the skin to enter the Table 3: Distribution of congenital anomalies according to the maternal characteristics bloodstream; however, there is a possibility of entry via the exposed injuries. (47) Although there is no considerable proof of hereditary defects resulting from the exposure of parents to DU, studies have indicated that exposure to DU causes a breakdown of DNA strands, which increases with the increasing concentration of radioactive particles left by DU munitions.…”

Section: Depleted Uraniummentioning

confidence: 99%

Post-war environmental pollution as a risk factor of congenital disorders in Iraq: A study review

Al-Hamdany

2019

IqNJM

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Background: Several years of war with the recent terrorist conflicts have cumulatively affected Iraq’s land, air, water, and health infrastructure, and a substantial rise in the incidence of congenital defects has been reported in the period following the Gulf War in 1991, which was principally accredited to the environmental contamination by depleted uranium. Aim: The aim is to review some published works of literature that are specifically concerned with environmental pollution after the war in Iraq as a possible risk factor for developmental disorders. Patients and Methods: In addition to the published articles, this review includes a direct descriptive data of congenital anomalies, which was obtained from Al-Khansaa, Al-Salaam, Al-Batool Teaching Hospitals of Obstetrics and Gynecology, and General Mosul Hospital in Mosul city over a period of 12 months, starting from October 2017 to October 2018. Results: All of the research related to this topic were discussed, and most of them revealed that a higher incidence of congenital disorders was detected among people exposed directly or indirectly to post-war environmental pollution by depleted uranium (DU) and other chemical constituents. From the analysis of the scientific publications, we observed that Basrah, Baghdad, Falluja, Mosul and Al-Anbar are predominantly affected by war contamination. The study revealed that there were 317 cases of birth defects out of the 44,372 newborns delivered over a period of one year after war in Mosul; thus, the overall percentage of congenital disorders was 0.71%, and defects of the nervous system were the most prominent, among which anencephaly was the predominant condition. The highest percentage of anomalies was detected in the maternal age of 21–26 and more in female newborns. Conclusion: We must decrease parental exposure to the possible teratogens through prenatal counseling and public education about the penalties of environmental pollution in order to arrange practical guidelines for public health and to alleviate the outcome of pregnancy. Keywords: pollution, congenital, post-war,environmental, review

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“…(45) The comprehensive mechanisms by which DU affects the metabolic functions of the human cells remain to be adequately explored, but many researchers have confidently suggested a cellular and molecular toxicity of DU. (46) Ingestion of food or drinking water contaminated by DU or the inhalation of contaminated air and dust are the most critical pathways of exposure to environmental DU for the general public, whereas direct dermal contact is an insignificant pathway because DU cannot permeate the skin to enter the bloodstream; however, there is a possibility of entry via the exposed injuries. (47) Although there is no considerable proof of hereditary defects resulting from the exposure of parents to DU, studies have indicated that exposure to DU causes a breakdown of DNA strands, which increases with the increasing concentration of radioactive particles left by DU munitions.…”

Section: Depleted Uraniummentioning

confidence: 99%

Untitled

2020

IqNJM

View full text Add to dashboard Cite

Background: Several years of war with the recent terrorist conflicts have cumulatively affected Iraq's land, air, water, and health infrastructure, and a substantial rise in the incidence of congenital defects has been reported in the period following the Gulf War in 1991, which was principally accredited to the environmental contamination by depleted uranium. Aim: The aim is to review some published works of literature that are specifically concerned with environmental pollution after the war in Iraq as a possible risk factor for developmental disorders. Patients and Methods:In addition to the published articles, this review includes a direct descriptive data of congenital anomalies, which was obtained from Al-Khansaa, Al-Salaam, Al-Batool Teaching Hospitals of Obstetrics and Gynecology, and General Mosul Hospital in Mosul city over a period of 12 months, starting from October 2017 to October 2018. Results: All of the research related to this topic were discussed, and most of them revealed that a higher incidence of congenital disorders was detected among people exposed directly or indirectly to post-war environmental pollution by depleted uranium (DU) and other chemical constituents. From the analysis of the scientific publications, we observed that Basrah, Baghdad, Falluja, Mosul and Al-Anbar are predominantly affected by war contamination. The study revealed that there were 317 cases of birth defects out of the 44,372 newborns delivered over a period of one year after war in Mosul; thus, the overall percentage of congenital disorders was 0.71%, and defects of the nervous system were the most prominent, among which anencephaly was the predominant condition. The highest percentage of anomalies was detected in the maternal age of 21-26 and more in female newborns. Conclusion: We must decrease parental exposure to the possible teratogens through prenatal counseling and public education about the penalties of environmental pollution in order to arrange practical guidelines for public health and to alleviate the outcome of pregnancy.

show abstract

Toxicity of depleted uranium complexes is independent of p53 activity

Cited by 10 publications

References 39 publications

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Inhibition of poly(ADP-ribose)polymerase-1 and DNA repair by uranium

Post-war environmental pollution as a risk factor of congenital disorders in Iraq: A study review

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