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

Journal Article · Sun May 01 04:00:00 EDT 2005 · Molecular Carcinogenesis

DOI:https://doi.org/10.1002/mc.20092· OSTI ID:15020547

Weber, Thomas J; Siegel, Robert W; Markillie, Lye Meng; Chrisler, William B; Lei, Xingye C; Colburn, Nancy H

Radiation at low doses (? 50 cGy) can enhance or reduce tumor incidence in the mouse skin multistage model of carcinogenesis, depending on the timing of radiation exposure relative to chemical initiator. Here we have used JB6 mouse epidermal cells, an in vitro model of late stage tumor promotion, to evaluate the effects of low dose gamma radiation on cell transformation response. JB6 cells were isolated from the DNA-dependent Protein Kinase (DNA-PK) deficient Balb/c mouse that exhibits an unusually sensitive mammary tumor response to ionizing radiation. Exposure of JB6 cells to low dose (2-20 cGy) gamma radiation increased cell transformation response in a dose- and cell density-dependent fashion. JB6 cells were transfected with a membrane targeted enhanced yellow fluorescent protein (EYFP-membrane) and used as bystander cells in a co-culture model. Co-culture of 10 cGy irradiated JB6 cells with na?ve EYFP-membrane cells resulted in a significant increase in EYFP-expressing colonies, relative to co-cultures of sham exposed P+ cells/na?ve EYFP-membrane cells. In contrast, low dose gamma radiation (20 cGy) reduced tumor promoter (epidermal growth factor; 12-O-tetradecanoyl phorbol-13-acetate)-induced transformation response and cell survival in a clonogenic assay to a comparable extent (40%). Our results demonstrate different selective pressures depending on whether low dose radiation modulated the cell transformation response of irradiated or bystander cells, or whether irradiation occurred in conjunction with tumor promoter treatment. The co-culture system developed here is a promising model to define positive and negative selective pressures induced by low dose radiation in a DNA damage repair deficient context that are relevant to carcinogenesis responses.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 15020547
• Report Number(s): PNNL-SA-41438
• Journal Information: Molecular Carcinogenesis, Journal Name: Molecular Carcinogenesis Journal Issue: 1 Vol. 43
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CARCINOGENESIS
CELL TRANSFORMATIONS
DNA DAMAGES
GAMMA RADIATION
GROWTH FACTORS
IN VITRO
IONIZING RADIATIONS
IRRADIATION
MEMBRANES
NEOPLASMS
PHOSPHOTRANSFERASES
POPULATIONS
PROTEINS
RADIATIONS
REPAIR
TRANSFORMATIONS
TUMOR PROMOTERS
bystander
paracrine
radiation
response
transformation