Altered steady-state levels of the messenger RNAs for c-myc and p53 in L1210 cell lines resistant to deoxyadenosine.
L1210 cell lines, selected for resistance to deoxyadenosine due to the loss of allosteric inhibition of ribonucleotide reductase by dATP, had altered steady-state levels of the mRNAs for c-myc, fos, and p53. Wild-type L1210 cells had constitutive steady-state levels of c-myc and p53 with little or no fos mRNA. Two different deoxyadenosine-resistant cell lines (Y8 and ED2) had elevated steady-state levels of c-myc and fos but essentially no p53 mRNA. Hydroxyurea-resistant L1210 cells had the same levels of c-myc, fos, and p53 as the wild-type cells. There was no amplification of the gene for c-myc in the Y8 or ED2 cell lines. The half-life for c-myc mRNA was essentially the same in the wild-type and the Y8 and ED2 cells. Nuclear runoff experiments showed that the rates of transcription for c-myc in the Y8 and ED2 cells were elevated and could account for the increased steady-state levels of c-myc in these two cell lines. The transcription rate for p53 mRNA was not decreased in the Y8 and ED2 cells and therefore did not account for the loss of the steady-state levels of p53 in the cells. Cycloheximide treatment of the Y8 and ED2 cells resulted in a marked increase in the steady-state p53 mRNA level, indicating that a protein which was rapidly turned over was responsible for the extremely short half-life of p53 mRNA in these two cell lines.
Cory
J G
JG
Department of Biochemistry, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Cory
A H
AH
Long
S D
SD
Carter
G L
GL
Johnson
C E
CE
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D003839:Deoxyadenosines / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics*; D016259:Genes, myc; D016158:Genes, p53; D014644:Genetic Variation; D007939:Leukemia L1210 / Q000235:genetics*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015183:Restriction Mapping; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D003839:Deoxyadenosines; D012333:RNA, Messenger; D003513:Cycloheximide