Access Type

Open Access Dissertation

Date of Award

January 2013

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biological Sciences

First Advisor

James D. Tucker

Abstract

Chapters 2 and 3:

Depleted Uranium (DU) is a high-density heavy metal that has been used in munitions since the 1991 Gulf War. DU is weakly radioactive and chemically toxic and long term exposure may cause adverse health effects. This study evaluates genotoxic effects of DU exposure in Gulf War I Veterans as a function of uranium (U) body burden by measuring chromosome damage in peripheral blood lymphocytes with the cytokinesis blocked micronucleus assay (CBMN) and fluorescence in situ hybridization (FISH) whole chromosome painting. Study subjects are Gulf War I Veterans exposed to DU during friendly fire incidents in 1991 involving DU munitions which resulted in inhalation and ingestion exposure to small particles of DU and soft tissue DU fragments from traumatic injuries. The Veterans are enrolled in a long term health surveillance program at the Baltimore VA Medical Center.

Evaluation of subjects using the CBMN assay:

Blood was drawn from 35 exposed male Veterans aged 36 to 59 years, then cultured and evaluated for micronuclei (MN). The participants were divided into two exposure groups, low and high, based on their mean urine Uranium concentrations. Poisson regression analyses with mean urine U concentrations, current smoking, X-rays in the past year and donor age as dependent variables revealed no significant relationships with MN frequencies. Our results indicate that ongoing systemic exposure to DU in Gulf War I Veterans with embedded DU fragments does not induce significant increases in MN in peripheral blood lymphocytes compared to MN frequencies in Veterans with normal urine Uranium levels.

Evaluation of subjects using FISH whole chromosome painting assay:

Blood was drawn from 35 exposed male Veterans aged 39 to 62 years, then cultured and harvested for metaphase chromosome analyses. Chromosomes 1, 2, and 4 were painted red and chromosomes 3, 5, and 6 were simultaneously labeled green. At least 1800 metaphase cells per subject were scored. Univariate regression analyses were performed to evaluate the effects of log(urine Uranium), age at time of blood draw, log(lifetime X-rays), pack-years smoked and alcohol use against frequencies of cells with translocated chromosomes, dicentrics, acentric fragments, color junctions and abnormal cells. No significant relationships were observed between any cytogenetic endpoint and log(urine Uranium) levels, smoking, or log(lifetime X-rays). Age at the time of blood draw showed significant relationships with all endpoints except for cells with acentric fragments. These results indicate that chronic exposure to DU does not induce significant levels of chromosome damage in these Veterans.

Chapter 4:

To determine the extent to which age influences individual susceptibility to ionizing radiation, blood samples were collected from 20 adults and from the umbilical cords of 10 newborns. Samples were acutely exposed to Cobalt 60 gamma rays to doses of 0 (control), 1, 2, 3 and 4 Gy. Cells in metaphase were labeled with whole chromosome paints and evaluated for structural chromosome aberrations. Regression analyses were used to evaluate the frequencies of each of the major classes of structural aberrations to determine whether susceptibility to radiation was dependent upon age. Compared to adults, blood from newborns showed statistically significant increases in translocated chromosomes, dicentrics, and color junctions for doses from 0 to 3 Gy, but not at 4 Gy. When adults were considered alone, no significant changes in radiation susceptibility were observed with age. The increased susceptibility of newborns to ionizing radiation, and the absence of any change in susceptibility during adulthood, should be relevant when making radiation-exposure risk assessments.

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