title: Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative.
abstract: A comparison was made of the ability of either X-radiation or a DNA-specific ligand (the vital bis-benzimidazole dye; Hoechst 33342) to induce: cell killing, inhibition of de novo DNA synthesis, DNA strand breakage and the delay of cell division in human colon adenocarcinoma cells in vitro. Unlike radiation-induced cell killing, ligand-induced cytotoxicity appeared to be positively correlated with the extent of inhibition of de novo DNA synthesis--a feature consistent with the persistent binding of ligand molecules to nuclear DNA. Ligand-induced DNA strand-breaks disappeared slowly although ligand-treated cells retained apparently normal capacities to repair discrete radiogenic DNA strand-breaks. Pre-treatment of cells with Hoechst 33342 resulted in a dose-modifying enhancement of radiation resistance not associated with altered dosimetry for strand-break induction. However, radioresistance was accompanied by the protracted retention of cells in the G2 phase of the cell cycle. We suggest that the results provide direct evidence that the retention of cells in G2 phase is a sparing phenomenon and is triggered by the responses of chromatin domains to the presence of DNA damage. Our results have implications for the use of DNA-interactive agents in combined modalities for tumour therapy, and indicate a possible basis for the sparing of some tumour cells in dividing populations.
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D001562:Benzimidazoles / Q000494:pharmacology* / Q000633:toxicity; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000096:biosynthesis; D006801:Humans; D011837:Radiation-Protective Agents; D014965:X-Rays
chemical_list: D001562:Benzimidazoles; D004273:DNA, Neoplasm; D011837:Radiation-Protective Agents; C017807:bisbenzimide ethoxide trihydrochloride