Cell Cycle-dependent Cytotoxicity of Alkylating Agents: Determination of Nitrogen Mustard-induced DNA Cross-Links and Their Repair in Chinese Hamster Ovary Cells Synchronized by Centrifugal Elutriation
作者： Raymond E. Meyn , David Murray
DOI:
关键词: Chlormethine 、 Clonogenic assay 、 Cytotoxicity 、 Chinese hamster ovary cell 、 DNA damage 、 Biology 、 Cell cycle 、 Genetics 、 Cell culture 、 Molecular biology 、 DNA
摘要: Abstract Chinese hamster ovary cells were synchronized into the different phases of cell cycle by centrifugal elutriation and treated with nitrogen mustard (HN2) in order to investigate role DNA damage repair processes cycle-dependent cytotoxicity this alkylating antitumor agent. In agreement previous studies, populations enriched G 1 most sensitive HN2, those late S phase-G 2 more resistant, as determined clonogenic assay. Although variation surviving fraction through response a single dose (3 µg/ml; 1.0 h) HN2 was great factor 10, complete dose-response curves generated for resistant elutriator fractions indicated that such changes could be accounted ratio D 0 values only 1.4. Cells same method also analyzed their relative levels HN2-induced cross-linking using technique alkaline elution. There no significant difference either interstrand or DNA-protein cross-links induced two described above immediately after treatment. When amount measured 6 h treatment, considerable had occurred; however, there measurable rate type cross-link ( i.e. , DNA-protein) phases. Differences not therefore resolved within confidence limits available assays probably cannot account differential towards
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