A paracrine signal mediates the cell transformation response to low dose gamma radiation in JB6 cells

Mol Carcinog. 2005 May;43(1):31-7. doi: 10.1002/mc.20092.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Bacterial Proteins / genetics
  • Cell Line
  • Cell Transformation, Neoplastic / radiation effects*
  • Coculture Techniques
  • Dose-Response Relationship, Radiation
  • Flow Cytometry
  • Gamma Rays*
  • Luminescent Proteins / genetics
  • Mice
  • Microscopy, Fluorescence

Substances

  • Bacterial Proteins
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria