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AFRL-HE-WP-TP-2006-0019Air Force Research Laboratory
Effect of Silver Nanoparticles on SRCActivity in Male Germ-Line Stem Cells
Laura K. Braydich-Stolle
University of DaytonDayton OH 45437-0009
Saber HussainJohn J. Schlager
Air Force Research LaboratoryHuman Effectiveness DirectorateApplied Biotechnology Branch
Wright-Patterson AFB OH 45433-5707
Marie-Claude Hofmann
University of DaytonDayton OH 45437-0009
March 2006
FINAL REPORT -JUNE 2003 TO SEPTEMBER 2005
20060403510Approved for public release; Air Force Research Laboratory
distribution unlimited Human Effectiveness Directorate
Biosciences and Protection DivisionApplied Biotechnology BranchWright-Patterson AFB, OH 45433-5707
Form ApprovedREPORT DOCUMENTATION PAGE OMB No. 0704-0188
Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining thedata needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducingthis burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currentlyvalid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS.
1. REPORT DATE (DD-MM-YYYY) 2. REPORT TYPE 3. DATES COVERED (From - To)
March 2006 Technical Paper June 2003 - September 20054. TITLE AND SUBTITLE 5a. CONTRACT NUMBEREffect of Silver Nanoparticles on SRC Activity in Male Germ- F33615-03-C-6325
Line Stem Cells 5b. GRANT NUMBER
5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S) 5d. PROJECT NUMBER*L.K. Braydich-Stolle; **Saber Hussain, **John J. Schlager, *Marie-Claude 2312
Hofmann 5e. TASK NUMBER
5f. WORK UNIT NUMBER
7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORTAND ADDRESS(ES) NUMBER*Air Force Materiel Command **University of
Air Force Research Laboratory DaytonHuman Effectiveness Directorate Daytotn OH AFRL-HE-WP-TP-2006-0019Wright-Patterson AFB OH 45433-7022
9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S)Air Force Materiel Command AFRL/HEPB
Air Force Research Laboratory
Human Effectiveness Directorate 11. SPONSORIMONITOR'S REPORT
Biosciences and Protection Division NUMBER(S)
Wright-Patterson AFB OH 45433-5707
12. DISTRIBUTION / AVAILABILITY STATEMENTApproved for public release; distribution is unlimited.
13. SUPPLEMENTARY NOTESThese are briefing charts. Clearance: AFRL/WS-06-0428, 15 Feb 06.
14. ABSTRACTGametogenesis is a complex biological process that is particularly sensitive to environmental insults such as chemicals and physicalstressors. Exposure to specific chemicals has been shown to inhibit fertility through a negative impact on germ cell proliferation anddifferentiation that can lower sperm count. In addition, toxicants might produce mutations that could have negative consequences on thedevelopment of the offspring. A previous study showed that a spermatogonial stem cell line, called C 18-4, provides a sensitive model toassess the cytotoxicity of nanoparticles in the male germ line. We also found that Ag-15nm was more toxic than Al-30nm and MoO3-30nmfor spermatogonial stem cell proliferation. The purpose of the present study was to determine the effects of various sizes of Agnanoparticles on the C18-4 cell line using standard cytotoxic assays. We also assessed the impact of Ag nanoparticles on Src signaling,since the activation of this kinase allows normal spermatogonial stem cells to proliferate. Mitochondrial function (MTS) data showed thatAg-130nm was not toxic to the cells, but smaller particles showed toxicity. Membrane leakage was increased by treatment with the Ag-25nm and Ag-30nm particles, even at low concentrations (5 pg/ml). However, no membrane leakage was apparent when the cells weretreated with Ag- 130nm. Further, we have found that the activity of Fyn (a member of the Src family of cytoplasmic kinases) issignificantly reduced when the cells are treated with Ag nanoparticles. This inhibition increases with the size of the nanoparticles, with noactivity detected above a size of 30 nm..15. SUBJECT TERMSUninhabited Systems16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18. NUMBER 19a. NAME OF RESPONSIBLE PERSON
Unclassified OF ABSTRACT OF PAGES Saber Hussain
a. REPORT b. ABSTRACT c. THIS PAGE UL 30 19b. TELEPHONE NUMBER (include area
UNC UNC UNC code)(937) 904-9517
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