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NASA Scientific and Technical Aerospace Reports

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20040111633 Jackson (Henry M.) Foundation, Rockville, MD<br />

Preconceptional Paternal Exposure to Embedded Depleted Uranium Fragments: Transmission of Genetic Damage to<br />

Offspring<br />

Miller, Alex<strong>and</strong>ra C.; Mar. 2004; 9 pp.; In English<br />

Contract(s)/Grant(s): DAMD17-02-1-0185<br />

Report No.(s): AD-A425734; No Copyright; Avail: CASI; A02, Hardcopy<br />

The Persian Gulf War resulted in friendly fire casualties among U.S. personnel injured by fragments of depleted uranium<br />

(DU) munitions. The demonstrated effectiveness of such weapons makes it likely that they may be used against U.S. forces<br />

in future conflicts. Uncertainty about how aggressively to remove fragments of the radioactive, chemically toxic DU has<br />

stimulated research into the long-term health consequences of embedded DU fragments. There has been no previous research<br />

to determine whether long-term exposure to embedded DU can affect the health of offspring of personnel wounded by DU.<br />

This study investigates whether male mice carrying embedded fragments of DU transmit genetic damage to their offspring.<br />

We hypothesize that long-term chronic exposure to embedded DU results in paternal transmission of genetic damage to<br />

unexposed Fl generation offspring, characterized by increased frequency of in vivo mutations in tissues. During this the second<br />

year of this project, we have completed metal (DU <strong>and</strong> tungsten) implantation surgeries, completed breeding of DU-implanted<br />

mice, completed neutron- irradiations, initiated breeding of tungsten-implanted mice, initiated the mutation assay <strong>and</strong> initiated<br />

the DNA damage assay to assess direct DNA damage in germ cells.<br />

DTIC<br />

Damage; Diseases; Embedding; Exposure; Genetics; Heavy Metals; Progeny; Spent Fuels; Tungsten Alloys; Uranium;<br />

Uranium Alloys<br />

20040111634 British Columbia Univ., Vancouver, British Columbia<br />

Experimental Treatment of Prostate Cancer Models with Rh2, An Isolated Ginsenoside Compound<br />

Xie, Xiaowei S.; Mar. 2004; 14 pp.; In English; Original contains color illustrations<br />

Contract(s)/Grant(s): DAMD17-02-1-0260<br />

Report No.(s): AD-A425735; No Copyright; Avail: CASI; A03, Hardcopy<br />

Ginseng is commonly used in herbal preparations for traditional Chinese medicine. Rh2, one of the ginsenosides, has been<br />

shown to suppress growth <strong>and</strong> induce apoptosis in a number of cancer cell lines both in vitro <strong>and</strong> in vivo. To evaluate the<br />

combined efficacy of Rh2 <strong>and</strong> two chemotherapeutic agents, paclitaxel <strong>and</strong> mitoxantrone, mice bearing the LNCaP or PC-3<br />

prostate tumor xenograft were treated with corn oil (po) <strong>and</strong> saline (iv), Rh2 (5Omg/kg po daily), paclitaxel (6 mg/kg iv on<br />

day 1, 4, 15, <strong>and</strong> 18), mitoxantrone (2.5 mg/kg iv on day 1, 4, 15, <strong>and</strong> 18), Rh2 + paclitaxel <strong>and</strong> Rh2 + mitoxantrone. Tumor<br />

volumes were measured twice weekly for 4 weeks. Serum PSA were tested using ELISA for LNCaP models. Results showed<br />

1) For the LNCaP models, student t-test was performed on the data acquired <strong>and</strong> results showed statistically significant<br />

differences exist between the tumor growth ratio of control group <strong>and</strong> Rh2+ paclitaxel treatment group (P\h0.05) from day 9.<br />

No statistical significant differences existed between the control group <strong>and</strong> the Rh2, paclitaxel or mitoxantrone monotreatment<br />

groups. Paclitaxel monotherapy <strong>and</strong> paclitaxel + Rh2 combination showed significant (p\hO.O5) <strong>and</strong> very significant<br />

(p\hO.Ol) inhibitory effect on serum PSA levels. 2) There was no statistically significant differences exist between PC-3 model<br />

groups treated with placebo, Rh2, Paclitaxel, mitoxantrone or combination. Overall, our results suggest that oral<br />

administration of Rh2 can sensitize low dose of Paclitaxel in the treatment of mice bearing subcutaneous LNCaP prostate<br />

tumors <strong>and</strong> exhibits potential as a chemosensitizer of paclitaxel for treatment of <strong>and</strong>rogen- dependent prostate cancer.<br />

DTIC<br />

Apoptosis; Cancer; In Vivo Methods <strong>and</strong> Tests; Prostate Gl<strong>and</strong><br />

20040111635 California Univ., Los Angeles, CA<br />

Endothelial Genes<br />

Nguyen, Mai H.; Jun. 2003; 18 pp.; In English; Original contains color illustrations<br />

Contract(s)/Grant(s): DAMD17-02-1-0330<br />

Report No.(s): AD-A425736; No Copyright; Avail: CASI; A03, Hardcopy<br />

The identification of novel endothelial-derived genes is important in the study of angiogenesis, <strong>and</strong> may have potential<br />

uses in cancer diagnosis <strong>and</strong> treatment. We performed SSH (suppression subtractive hybridization) on control HUVECs<br />

(human umbilical vein endothelial cells) versus HUVECs exposed to tumor-conditioned media. We found that a novel cDNA<br />

(Genbank accession # AF358829) is differentially expressed in endothelial cells on Northern analysis, <strong>and</strong> named it<br />

Endothelial-derived gene-1 (EG-1). This gene product is predicted to encode a 178-aa, 19.5 kD protein, <strong>and</strong> is localized to<br />

chromosome #4. It has some homology to a mouse cDNA (94%) <strong>and</strong> a Drosophila cDNA (31%). On Northern analysis,<br />

193

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