Molecular events in radiation transformation
Studies of human tumor cell lines have revealed alterations in the regulation of a number of cell cycle-related genes, associated in some cases with a TP53-independent loss of the radiation-induced G(1)-phase arrest. It is not clear, however, whether these are early or late events in tumor developme...
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Published in | Radiation research Vol. 155; no. 1 Pt 2; p. 215 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
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United States
01.01.2001
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Abstract | Studies of human tumor cell lines have revealed alterations in the regulation of a number of cell cycle-related genes, associated in some cases with a TP53-independent loss of the radiation-induced G(1)-phase arrest. It is not clear, however, whether these are early or late events in tumor development, or they arise in tumor cell lines during growth in culture. Since the oncogenic transformation of an individual cell is thought to be an early event in tumor development, we have used a model system of normal and radiation-transformed C3H 10T(1/2) mouse fibroblast cell clones to address this issue. Transformed clones derived from type III foci were compared with clones derived from parental, wild-type cells. Approximately 25% of transformed clones showed Trp53 mutations in exon 5; however, preliminary results based on in situ immunofluorescence studies with an antibody recognizing mutant Trp53 indicate that the appearance of such mutations in transformed clones occurs late in the process of transformation and is unlikely to represent an initiating event. The remaining transformed clones and all clones derived from parental cells expressed wild-type Trp53. Radiation-induced G(1)-phase arrest was either absent or significantly reduced in all of the transformed clones, independent of Trp53 status. Constitutive expression of Cdkn1a protein was significantly increased in most of the transformed clones. Also, the majority of transformed clones showed elevated levels of cyclin D1, and two clones overexpressed cyclin E. These results indicate that loss of G(1)-phase checkpoint control, independent of Trp53 status, and altered expression of cell cycle regulatory proteins may represent early events in the process of radiation-induced carcinogenesis that are associated with the malignant transformation of individual cells. |
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AbstractList | Studies of human tumor cell lines have revealed alterations in the regulation of a number of cell cycle-related genes, associated in some cases with a TP53-independent loss of the radiation-induced G(1)-phase arrest. It is not clear, however, whether these are early or late events in tumor development, or they arise in tumor cell lines during growth in culture. Since the oncogenic transformation of an individual cell is thought to be an early event in tumor development, we have used a model system of normal and radiation-transformed C3H 10T(1/2) mouse fibroblast cell clones to address this issue. Transformed clones derived from type III foci were compared with clones derived from parental, wild-type cells. Approximately 25% of transformed clones showed Trp53 mutations in exon 5; however, preliminary results based on in situ immunofluorescence studies with an antibody recognizing mutant Trp53 indicate that the appearance of such mutations in transformed clones occurs late in the process of transformation and is unlikely to represent an initiating event. The remaining transformed clones and all clones derived from parental cells expressed wild-type Trp53. Radiation-induced G(1)-phase arrest was either absent or significantly reduced in all of the transformed clones, independent of Trp53 status. Constitutive expression of Cdkn1a protein was significantly increased in most of the transformed clones. Also, the majority of transformed clones showed elevated levels of cyclin D1, and two clones overexpressed cyclin E. These results indicate that loss of G(1)-phase checkpoint control, independent of Trp53 status, and altered expression of cell cycle regulatory proteins may represent early events in the process of radiation-induced carcinogenesis that are associated with the malignant transformation of individual cells. |
Author | Krolewski, B Syljuåsen, R G Little, J B |
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BackLink | https://www.ncbi.nlm.nih.gov/pubmed/11121237$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Animals Cell Line, Transformed Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - pathology Cell Transformation, Neoplastic - radiation effects Cyclin-Dependent Kinase Inhibitor p21 Cyclins - biosynthesis Cyclins - genetics Fibroblasts - cytology Fibroblasts - radiation effects G1 Phase - radiation effects Genes, cdc - radiation effects Genes, p53 - radiation effects Mice Mice, Inbred C3H Mutation Neoplasms, Radiation-Induced - genetics Neoplasms, Radiation-Induced - pathology Tumor Suppressor Protein p53 - biosynthesis Tumor Suppressor Protein p53 - genetics |
Title | Molecular events in radiation transformation |
URI | https://www.ncbi.nlm.nih.gov/pubmed/11121237 |
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