Cellular radiosensitivity, radioresistant DNA synthesis, and defect in radioinduction of p53 in fibroblasts from atherosclerosis patients
| Autor: | Sultan T. Al-Sedairy, Mohammed Kunhi, Pulicat S. Manogaran, Mohammed A. Hannan, David Sigut, Nargis Nasrin, Layth Mimish |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Adult
Cyclin-Dependent Kinase Inhibitor p21 Male Arteriosclerosis Cell Survival Biology Polymerase Chain Reaction Radiation Tolerance chemistry.chemical_compound Ataxia Telangiectasia Cyclins medicine Humans Radiosensitivity Fibroblast Cells Cultured Polymorphism Single-Stranded Conformational Aged Cellular radiosensitivity Cell Cycle Cancer DNA Fibroblasts Middle Aged medicine.disease Flow Cytometry medicine.anatomical_structure chemistry Gamma Rays Immunology Cancer research Radioresistant DNA synthesis Female Tumor Suppressor Protein p53 Cardiology and Cardiovascular Medicine |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 17(5) |
| ISSN: | 1079-5642 |
| Popis: | Abstract Earlier studies have suggested that both cancer and atherosclerosis may follow a common pathway in the early stage of development and share certain risk factors. One report indicated that the gene responsible for the radiosensitive, cancer-prone, multisystem disorder ataxia telangiectasia (AT) may increase the risk of developing ischemic heart disease. The present studies were carried out to find similarities, if any, between atherosclerosis patients and AT homozygotes or heterozygotes (ATHs) in their cellular/molecular response to ionizing radiation, which acts as a carcinogen as well as an atherogen. Fibroblast cell strains developed from healthy subjects and from AT homozygotes, ATHs, and atherosclerosis patients were compared for (1) survival, by the colony-forming assay and (2) DNA synthesis inhibition after irradiation, determined by [ 3 H]thymidine incorporation, cell cycle distribution, and the expression of p 53 and p 21 proteins, analyzed by flow cytometry. Fibroblasts from the atherosclerosis patients as a group, compared with the healthy subjects, showed enhanced sensitivity to chronic (low-dose-rate) irradiation. A majority of the cell strains representing atherosclerosis patients exhibited varying degrees of radioresistant DNA synthesis (RDS), with roughly 33% showing an AT-like and the rest an ATH-like response. All cell strains with an AT-like and one quarter with an ATH-like RDS were found to be defective in the radioinduction of both p 53 and p 21 proteins, which are concerned with cell cycle regulation. An absence of G 1 arrest after irradiation was observed in cell strains lacking a radioinduced expression of p 53 and p 21 . Cellular/ molecular defects leading to increased radiosensitivity, reduced induction of p 53 /p 21 , and cell cycle deregulation found to be associated with cancer-prone disorders such as AT may constitute important risk factors for atherosclerosis as well. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|