Early induction of CDKN1A (p21) and GADD45 mRNA by a low dose of ionizing radiation is due to their dose-dependent post-transcriptional regulation.
Previous studies have shown that induction of some genes by low-dose radiation has a different dependence on the time after irradiation than induction by high doses. To examine the mechanisms underlying this phenomenon, we investigated the changes in the time course of the rates of transcription of genes in cells of the human myeloblastic leukemia cell line ML-1 by a nuclear run-on assay. It is possible that the more rapid induction of the mRNA of the CDKN1A and GADD45 genes after exposure to 50 cGy of X rays than after 20 Gy is due to a lower level of stabilization of the mRNA of these genes after 50 cGy. In addition, our results show that 50 cGy of X rays increases the transcription rates of the CDKN1A and GADD45 genes, with a maximum induction at 0.5 to 1 h after irradiation, much earlier than the maximum accumulation of stabilized TP53 protein. We suggest the involvement of BRCA1 protein in the early induction of transcription of these two genes.
Daino
Kazuhiro
K
Department of Biology, Faculty of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Ichimura
Sachiko
S
Nenoi
Mitsuru
M
D015153:Blotting, Western; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects*; D014407:Tumor Cells, Cultured; D000097642:GADD45 Proteins
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D000097642:GADD45 Proteins; C493956:CDKN1A protein, human