Identification and characterization of soluble factors in delayed effects of low dose radiation
EMSL Project ID
3523a
Abstract
There is compelling evidence from in vitro tissue culture studies, in vivo animal models, irradiated human subjects, and radiotherapy patients, for a variety of biological effects occurring outside the radiation field and to the progeny of irradiated cells. An understanding these non-targeted mechanisms of radiation damage is needed for reliable assessment of the health risks from low-level exposure to ionizing radiation. We will use proteome-wide high throughput mass spectrometry to identify and quantify soluble factor released by chromosomally unstable clones of the human/hamster hybrid cells line GM10115, which are the progeny of cells that survived radiation exposure. Special focus will be given to factors responsible for the death inducing effect (DIE) when media conditioned by the growth of unstable GM10115 cells is placed over the parental cell line. Three specific aims are proposed. In Aim (1) we will biochemically characterize the DIE response, identify the released factor(s), and estimate relative abundances for factors potentially responsible for DIE. In Aim (2) we will integrate the experimental data from Aim 1 with existing pathway knowledge and use this information to design reconstitutions experiments to validate candidate proteins involved in DIE. In Aim (3) we will obtain proof of principal that candidate factor(s) identified in Aims 1 and 2 modulate the cytotoxicity in parental GM10115 cells.
Project Details
Project type
Exploratory Research
Start Date
2007-03-22
End Date
2008-03-23
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members