Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation.
Normal human fibroblast (i.e., GM2936B, GM2907A, and IMR-90) and cancer-prone human fibroblast (i.e., Fanconi's anemia, Bloom's syndrome, and Ataxia telangiectasia) cells demonstrated the induction of intracellular and extracellular levels of tissue-type plasminogen activator (t-PA) at 6 and 12 hr, respectively, following ionizing radiation. Induced t-PA enzymatic activities following ionizing radiation were blocked by actinomycin D treatments. t-PA enzymatic activities were induced over 14-fold in Ataxia telangiectasia cells, over 9-fold in Bloom's syndrome cells, and over 6-fold in Fanconi's anemia cells, as compared to normal human fibroblasts. Similarly, the induction of t-PA mRNA levels in cancer-prone cells were between 5- to 10-fold higher than those observed in normal cells following equitoxic doses of ionizing radiation. Temporal induction of t-PA mRNA levels for normal and cancer-prone human cells were consistent with quantifiable enzymatic activities. The elevated induction of an intracellular protease (i.e., t-PA) in cancer-prone human cells is reminiscent of an "SOS"-like response observed in yeast and bacteria.
Fukunaga
N
N
Department of Radiation Oncology, University of Michigan, Ann Arbor 48109.
Burrows
H L
HL
Meyers
M
M
Schea
R A
RA
Boothman
D A
DA
D001260:Ataxia Telangiectasia / Q000201:enzymology; D001816:Bloom Syndrome / Q000201:enzymology; D002478:Cells, Cultured; D004260:DNA Repair; D005199:Fanconi Anemia / Q000201:enzymology; D005347:Fibroblasts / Q000201:enzymology / Q000528:radiation effects; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D011839:Radiation, Ionizing; D013014:SOS Response, Genetics; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator