Purpose: Human diseases associated with acute radiation responses are rare genetic disorders with common clinical and biological features including radiosensitivity, genomic instability, chromosomal aberrations, and frequently immunodeficiency. To determine what molecular assays are predictive of cellular radiosensitivity whatever the genes mutations, the existence of a quantitative correlation between cellular radiosensitivity and unrepaired DNA double-strand breaks (DSB) repair defects was examined in a collection of 40 human fibroblasts representing 8 different syndromes.
Materials And Methods: A number of techniques such as pulsed-field gel electrophoresis, plasmid assay and immunofluorescence with antibodies against MRE11, MDC1, 53BP1 and phosphorylated forms of H2AX, DNA-PK were applied systematically.
J Fam Plann Reprod Health Care
January 2007
Background And Purpose: There is still confusion in the choice of the molecular assays to predict the radiation response of human cells. The case of tumours appears to be particularly complex, may be because of their instability and heterogeneity. The aim of this study was to investigate quantitatively the relationships between DNA double-strand breaks (DSB) repair, chromatin relaxation and cellular radiosensitivity.
View Article and Find Full Text PDFFrequent deregulation of cyclin-dependent kinase (CDK) activation associated with loss of cell cycle control was found in most of human cancers. A recent development of a new class of antineoplasic agents targeting the cell cycle emerged as a small molecule CDK inhibitor, roscovitine, which presents potential antiproliferative and antitumoral effects in human tumors. Additional studies reported that roscovitine combined with cytotoxic agents can cooperate with DNA damage to activate p53 protein.
View Article and Find Full Text PDFPurpose: Stable chromosomal aberrations (SCAs) have been found in circulating lymphocytes from patients treated for breast carcinoma. Therefore, we tried to define their incidence in such patients, to determine an in vitro dose-effect relationship, and to correlate these data with clinical parameters.
Methods And Materials: This prospective study included 25 patients who, after surgery, underwent either radiotherapy (RT) alone (n = 15) or RT combined with chemotherapy (n = 10).