TY - JOUR
T1 - Enhanced induction of tissue-type plasminogen activator in normal human cells compared to cancer-prone cells following ionizing radiation
AU - Fukunaga, Nina
AU - Burrows, Heather L.
AU - Meyers, Mark
AU - Schea, Randi A.
AU - Boothman, David A.
N1 - Funding Information:
Presented at the 33rd Annual Meeting of American Society of Therapeutic Radiology and Oncology, Washington, D.C., 4 November 199 I. Reprint requests to: David A. Boothman, Ph.D., Dept. of Radiation Oncology, Division of Cancer Biology, University of Michigan Medical Center, 133 1 East Ann St., Rm. #4 13 1, Ann Arbor, MI 48 109, USA. Acknowledgments-The authors wish to thank Meizhi Wang, M.D. for her technical assistance on various experiments. Supported by Grant #PDT-4 12 to D.A.B. from the American Cancer Society and by Grant #DE-FGO2-9 1 ER6 1256 to D.A.B. from the U.S. Department of Energy. Accepted for publication 6 July 1992.
PY - 1992
Y1 - 1992
N2 - 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.
AB - 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.
KW - Ataxia telangiectasia
KW - Bloom's syndrome
KW - Fanconi's anemia
KW - Ionizing radiation
KW - SOS response
KW - tissue-type plasminogen activator
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U2 - 10.1016/0360-3016(92)90479-2
DO - 10.1016/0360-3016(92)90479-2
M3 - Article
C2 - 1447036
AN - SCOPUS:0026492150
SN - 0360-3016
VL - 24
SP - 949
EP - 957
JO - International journal of radiation oncology, biology, physics
JF - International journal of radiation oncology, biology, physics
IS - 5
ER -