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A paracrine signal mediates the cell transformation response to low dose gamma radiation in JB6 cells
Author(s) -
Weber Thomas J.,
Siegel Robert W.,
Markillie Lye M.,
Chrisler William B.,
Lei Xingye C.,
Colburn Nancy H.
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20092
Subject(s) - bystander effect , paracrine signalling , biology , microbiology and biotechnology , cell culture , transfection , transformation (genetics) , cell , immunology , receptor , biochemistry , genetics , gene
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 × 10 4 or 1 × 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. © 2005 Wiley‐Liss, Inc.