Stress-gene induction by low-dose gamma irradiation.
Using a human myeloid tumor cell line (ML-1), we detected induction of mRNA expression of several stress-responsive genes by doses of gamma rays as low as 2 cGy. For instance, the dose response for induction of CIP1/WAF1 and GADD45 appears to be linear over the range of 2 to 50 cGy and shows no evidence of a threshold for induction. Although 2 and 5 cGy exposures did not result in any detectable reduction in cloning efficiency nor in increased apoptosis in ML-1 cells, these exposures did produce a brief cell-cycle delay. We also used fluorescent cDNA microarray hybridization to investigate transcriptional stress responses following low doses of gamma rays and to identify additional radiation-responsive genes for inclusion in a stress-specific microarray we are developing. These studies provide insight into the molecular responses to physiologically relevant doses, which cannot necessarily be extrapolated from high-dose studies. The use of high throughput arrays will allow the identification of multiple stress-responsive genes that are radiation inducible in a variety of cell types and tissues. The expectation is that transcriptional stress responses will provide a molecular approach to monitoring for radiation exposure and detecting interindividual differences.
Fornace
Albert J
AJ
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Amundson
Sally A
SA
Do
Khanh T
KT
Meltzer
Paul
P
Trent
Jeffrey
J
Bittner
Michael
M
D005720:Gamma Rays; D005786:Gene Expression Regulation; D006801:Humans; D011829:Radiation Dosage; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured