Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays.
Recent results using very low doses of radiation have suggested that there is a hypersensitive region where cultures show an enhanced level of cell killing leading to a non-monotonic survival curve. This effect has been observed at doses below 2 Gy in mammalian systems and at much higher doses in insect cells. In this paper we report observation of the effect in primary human uroepithelial cell cultures. The effect was measured using a postirradiation proliferation assay where irradiated explants of standard size were allowed to proliferate for 14 days after exposure to 60Co gamma irradiation. By 14 days the majority of cultures derived from explants irradiated with 2-5 Gy showed little evidence of growth inhibition and cell numbers approached or even exceeded those obtained in the controls. There was, however, a significant reduction in cell number and growth rate in all cultures exposed to doses lower than 1 Gy. Oncoprotein (p53, c-myc, bcl-2, p21 ras) and EGFR expression were also measured in these cultures and were significantly increased. Morphological evidence of apoptosis was present in all irradiated cultures at 4 h after exposure, but this persisted for longer periods in cultures exposed to low doses.
Mothersill
C
C
Department of Physics, Dublin Institute of Technology, Ireland.
Harney
J
J
Lyng
F
F
Cottell
D
D
Parsons
K
K
Murphy
D M
DM
Seymour
C B
CB
D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D003037:Cobalt Radioisotopes; D004307:Dose-Response Relationship, Radiation; D004848:Epithelium / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D016283:Proto-Oncogene Proteins p21(ras) / Q000032:analysis; D011836:Radiation Tolerance; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D014551:Urinary Tract / Q000473:pathology / Q000528:radiation effects
D003037:Cobalt Radioisotopes; D016159:Tumor Suppressor Protein p53; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)