A model for the effect of excision repair on the survival of human cells exposed to chemical carcinogens.

Abstract:

: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.

journal_name

Chem Biol Interact

authors

Miller JH,Heflich RH

doi

10.1016/0009-2797(82)90005-9

subject

Has Abstract

pub_date

1982-03-01 00:00:00

pages

45-55

issue

1

eissn

0009-2797

issn

1872-7786

pii

0009-2797(82)90005-9

journal_volume

39

pub_type

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