title: A paracrine signal mediates the cell transformation response to low dose gamma radiation in JB6 cells.
abstract: The carcinogenic response to radiation is complex and may involve adaptive cellular responses as well as a bystander effect mediated by paracrine or intercellular signaling activities. Using a newly developed co-culture model we have examined whether low dose gamma radiation induces the transformation of JB6 mouse epidermal cells as well as non-irradiated bystander cells. Cell transformation response is defined as the acquisition of anchorage-independent growth properties and is quantified by counting colonies on soft agar. Exposure of JB6 cells to low dose (2-20 cGy) gamma radiation resulted in an approximate 1.9 +/- 0.1 and 2.8 +/- 0.5-fold increase in cell transformation response when cells were seeded at 1 x 10(4) or 1 x 10(5) cells/dish, relative to respective sham exposed controls. We developed a co-culture model where sham exposed or irradiated JB6 cells were mixed with non-irradiated JB6 cells that had been stably transfected with the enhanced yellow fluorescent protein (EYFP) to enable the distinction of fluorescent bystander-specific colonies. A significant increase in the number of bystander-specific colonies was observed in co-culture with 10 cGy irradiated JB6 cells (224 +/- 9), relative to the number of bystander-specific colonies arising in co-culture with sham exposed JB6 cells (55 +/- 16). Our results indicate that low dose radiation induces the transformation of JB6 cells and that a soluble paracrine factor that is secreted by irradiated cells induces the transformation of non-irradiated bystander cells.
authors.affiliation: Cell Biology and Biochemistry, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Weber
authors.forename: Robert W
authors.initials: RW
authors.lastname: Siegel
authors.forename: Lye M
authors.initials: LM
authors.lastname: Markillie
authors.forename: William B
authors.initials: WB
authors.lastname: Chrisler
authors.forename: Xingye C
authors.initials: XC
authors.lastname: Lei
authors.forename: Nancy H
authors.initials: NH
authors.lastname: Colburn
mesh_terms: D000818:Animals; D017209:Apoptosis; D001426:Bacterial Proteins / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D018920:Coculture Techniques; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D005720:Gamma Rays; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008856:Microscopy, Fluorescence
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria