University of California - Davis Cancer Center

Funding for Human Subjects Research:

DOE: Office of Biological and Environmental Research (OBER)

$50,000.00 (Est.) for: Fiscal Year 2005
Percent of funding associated with the use of human subjects: 61-80

Information on Use of Human Subjects:

This project does not involve the use of multiple protocols/subprojects.

Institutional Review Board (IRB) Review:
Type of Review: Full Board
Approving Institution: University of California - Davis Cancer Center
Most recent approval: 07/26/05
IRB approval number: 200311085-2

Number of human subjects who participated in this project/protocol/subproject in the last reporting period: 10
Reporting period for number of human subjects: Fiscal Year 2005

Type(s) of Human Subjects Involvement:

External use of ionizing radiation on human subjects:

• For clinical research
• Other. Explain:

Standard radiation therapy given and biopsy taken for skin analysis.

Collection of personally identifiable bodily materials (blood or blood products, urine, cells, tissue, teeth, organs, excreta, etc):

• Using cells cultured in a laboratory.
• Using bodily materials collected specifically for this project.

Other types of human subjects involvement. Explanation:

Collection of human skin resected for aesthetic purposes that is unlinked from any identifying data and otherwise would be discarded.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

Several investigations have demonstrated that significant biological effects can occur in animals, animal cells, immortalized human cell lines, and primary human cells after exposure to doses of ionizing radiation (IR) in the <1-10 cGy region. Little information, however, is available as to how observations made with cultured cells mimic or even pertain to the actual in vivo condition, especially in humans. Yet, such knowledge is ultimately required for reducing the uncertainty of assessing human risks due to low dose IR (LDIR) exposures, as may be encountered in a variety of environmental scenarios. Toward filling this information void, the project uses biopsied tissues from informed and consenting volunteers who are to receive radiation therapy for treatment of their prostate cancers. Modern dosimetry utilizing computerized tomography based 3-dimensional radiation treatment planning and PEREGRINE Monte Carlo treatment planning provides accurate calculations of radiation dose delivered to target tissue and peripheral tissue outside of the high dose region. The target volume receives therapeutic dose, e.g., 2 Gy, whereas tissue sites and volumes that receive far lesser doses, i.e., 1 to 10 cGy, can be defined, biopsied, and subjected to further study ex-vivo along with tissue samples from the primary target sites.

Risks to the patients are related only to the 3 mm core skin biopsies and thus are minimal. All patients give informed consent for the biopsy procedure, and confidentiality is maintained as no information is reported in any way to identify the individual patient. This in vivo exposure system can also provide information on adaptive or other responses after repeated exposures since patients receiving radiation with curative intent are radiated daily, five days a week, for six to eight weeks. A further advantage of using patient biopsies is that of gaining insight into the cellular and molecular responses to very low dose IR in normal tissue, i.e., three dimensionally configured in an otherwise undisturbed microenvironment with intact vasculature. Further, freshly explanted tissue samples can be subjected to additional manipulation, like re-irradiations with higher dose IR.