TY - JOUR
T1 - UV but not 2c-irradiation induces specific transcriptional activity of p53 in primary hepatocytes
AU - Bellamy, Christopher O.C.
AU - Prost, Sandrine
AU - Harrison, David J.
N1 - Copyright:
Copyright 2004 Elsevier Science B.V., Amsterdam. All rights reserved.
PY - 1997/10
Y1 - 1997/10
N2 - The mechanisms are poorly understood by which p53 can stimulate different downstream events, including growth arrest, DNA repair, and apoptosis, after DNA damage. Changes in protein levels do not predict a particular p53 response, but it is possible that differences in functional activities such as transactivation are important. The present report describes the successful use of a specific p53 reporter plasmid transfected into primary murine hepatocytes to evaluate p53 transactivation activity over time after two different genotoxic injuries (γ-irradiation, 15 Gy and UV-c irradiation, 10 J/m2) known to produce p53-dependent growth arrest in this cell type. The results show that UV injury to hepatocytes was followed by a transient increase in transcriptional activation of the reporter plasmid by p53 and that this response preceded changes in p53 protein levels, as assessed by immunocytochemistry. By contrast, γ-irradiation injury failed to induce detectable changes in either transactivation activity or hepatocyte p53 protein levels. The data show that p53 responses to DNA damage are dependent on both cell and injury type and suggest that in hepatocytes they can be independent of protein concentration and specific transcriptional activity. The results have implications for how particular dysfunctional p53 mutations in carcinogenesis could alter hepatocyte responses to different DNA injuries.
AB - The mechanisms are poorly understood by which p53 can stimulate different downstream events, including growth arrest, DNA repair, and apoptosis, after DNA damage. Changes in protein levels do not predict a particular p53 response, but it is possible that differences in functional activities such as transactivation are important. The present report describes the successful use of a specific p53 reporter plasmid transfected into primary murine hepatocytes to evaluate p53 transactivation activity over time after two different genotoxic injuries (γ-irradiation, 15 Gy and UV-c irradiation, 10 J/m2) known to produce p53-dependent growth arrest in this cell type. The results show that UV injury to hepatocytes was followed by a transient increase in transcriptional activation of the reporter plasmid by p53 and that this response preceded changes in p53 protein levels, as assessed by immunocytochemistry. By contrast, γ-irradiation injury failed to induce detectable changes in either transactivation activity or hepatocyte p53 protein levels. The data show that p53 responses to DNA damage are dependent on both cell and injury type and suggest that in hepatocytes they can be independent of protein concentration and specific transcriptional activity. The results have implications for how particular dysfunctional p53 mutations in carcinogenesis could alter hepatocyte responses to different DNA injuries.
KW - DNA damage
KW - Gamma irradiation
KW - Liver
KW - P53
KW - Reporter plasmid
KW - UV irradiation
UR - http://www.scopus.com/inward/record.url?scp=0030612987&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1096-9896(199710)183:2<177::AID-PATH909>3.0.CO;2-E
DO - 10.1002/(SICI)1096-9896(199710)183:2<177::AID-PATH909>3.0.CO;2-E
M3 - Article
C2 - 9390030
AN - SCOPUS:0030612987
SN - 0022-3417
VL - 183
SP - 177
EP - 181
JO - Journal of Pathology
JF - Journal of Pathology
IS - 2
ER -