A MODEL FOR THE EFFECT OF EXCISION REPAIR ON THE SURVIVAL OF HUMAN-CELLS EXPOSED TO CHEMICAL CARCINOGENS

被引：4

作者：

MILLER, JH ^{[1
]}

HEFLICH, RH ^{[1
]}

机构：

[1] NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 1982年 / 39卷 / 01期

关键词：

D O I：

10.1016/0009-2797(82)90005-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 1st-order process with 37% of the adducts remaining after .apprx. 70 h. From this information and the dose-response relationship for survival of NF and repair deficient cells it is possible to 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, the model can be used 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.

引用

页码：45 / 55

页数：11

共 14 条

[1]

AMACHER DE, 1977, P NATL ACAD SCI USA, V74, P1533

[2] REPAIR OF DNA DAMAGED BY ALKYLATING CARCINOGENS IS DEFECTIVE IN XERODERMA PIGMENTOSUM-DERIVED FIBROBLASTS [J].