Induction of stress genes by low doses of gamma rays.
Using cells of a human myeloid tumor cell line (ML-1), we have detected induction of several stress-responsive genes by doses of gamma rays below 50 cGy. We found a linear dose-response relationship for induction of CDKN1A (formerly known as CIP1/WAF1) and GADD45 mRNA levels over the range of 2-50 cGy, with no evidence of a threshold for induction. Although exposures to 2 and 5 cGy did not result in any detectable reduction in cloning efficiency or increased apoptosis in ML-1 cells, these exposures did produce a transient delay of cells in the phases of the cell cycle in addition to the observed up-regulation of CDKN1A and GADD45. The relative induction of genes such as CDKN1A by radiation doses that produce little toxicity indicates that surviving cells do contribute significantly to the observed stress responses. These studies should provide insight into the molecular responses to physiologically relevant doses that cannot necessarily be extrapolated from high-dose studies.
Amundson
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SA
National Institutes of Health, National Cancer Institute, Division of Basic Science, Bethesda, Maryland 20892, USA.
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Fornace
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D051696:Activating Transcription Factors; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015973:Gene Expression Regulation, Leukemic / Q000528:radiation effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007951:Leukemia, Myeloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein; D000097642:GADD45 Proteins
D051696:Activating Transcription Factors; D001798:Blood Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger; D014157:Transcription Factors; D051028:bcl-2-Associated X Protein; D000097642:GADD45 Proteins; C493956:CDKN1A protein, human; C497206:MDM2 protein, human