A model for the effect of excision repair on the survival of human cells exposed to chemical carcinogens.
A model is presented which correlates the survival of normal human fibroblasts (NF) after exposure to N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) with the rate of excision of carcinogen residues bound to DNA. Measurements of the rate of excision of carcinogen residues suggest that this is a first-order process with 37% of the adducts remaining after about 70 h. From this information and the dose-response relationship for survival of NF and repair deficient cells we can determine the mean number of adducts required to produce a potentially lethal lesion and the effective time available for repair. When these adjustable parameters have been determined, we can use the model to predict the rate of excision in partially repair-deficient cells and the effect of extending the repair period by arresting cell growth after treatment. Survival studies in which cells were held at confluence for varying amounts of time between treatment and replating at low density show good agreement with the predictions of the model.
D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004260:DNA Repair; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D012969:Sodium Fluoride / Q000494:pharmacology
D002273:Carcinogens; D000099:Acetoxyacetylaminofluorene; D012969:Sodium Fluoride