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Title: Modeling the dose-response relationship for cytotoxicity of human cells exposed to chemical carcinogens. [N-acetoxy-2-acetylaminofluorene]

Abstract

Compounds like N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) result from the in vivo reduction of nitrate derivatives of benzo(..cap alpha..)pyrene. The dose-response relationship for survival of cloning ability in human fibroblasts exposed to N-AcO-AAF is being investigated to obtain a better understanding of the carcinogenic potential of coal-related air pollutants. A model is presented which correlates the survival of normal human fibroblasts after exposure to N-AcO-AAF with the rate of excision of carcinogen residues bound to DNA. The model predicts that the survival of normal cells, S/sub N/, is related to the survival of repair deficient cells, S/sub XPA/, by the equation 1n(S/sub N/) = 1n(S/sub XPA/) (1-f) where f is the fraction of potentially lethal damage repaired in the normal cell at a given dose of carcinogen. The rate of excision of AAF residues from the DNA of confluent human fibroblasts was measured over the same dose range as the survival studies. This information together with the dose-response relationship for survival of normal and repair deficient cells permits a determination of the mean number of adducts required to produce a potentially lethal lesion and the effective time available for repair. The model can be used to predict the mean lifetime of carcinogen residuesmore » on the DNA of partially repair deficient cells and the effect of recovery on the survival of normal cells. Extensions of the model to account for shoulders on the dose-response relationship curves are also discussed.« less

Authors:
;
Publication Date:
Research Org.:
Battelle Pacific Northwest Labs., Richland, WA (USA); National Center for Toxicological Research, Jefferson, AR (USA)
OSTI Identifier:
7056145
Report Number(s):
PNL-SA-8679; CONF-801039-5
DOE Contract Number:  
AC06-76RL01830
Resource Type:
Conference
Resource Relation:
Conference: 20. annual Hanford Life Sciences symposium, Richland, WA, USA, 19 Oct 1980
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; 59 BASIC BIOLOGICAL SCIENCES; 01 COAL, LIGNITE, AND PEAT; CARCINOGENS; TOXICITY; DNA; BIOLOGICAL REPAIR; DOSE-RESPONSE RELATIONSHIPS; MATHEMATICAL MODELS; FIBROBLASTS; SURVIVAL CURVES; ORGANIC FLUORINE COMPOUNDS; XP CELLS; ADDUCTS; BIOCHEMICAL REACTION KINETICS; CELL CULTURES; EXPERIMENTAL DATA; MAN; THEORETICAL DATA; TIME DEPENDENCE; ANIMAL CELLS; ANIMALS; BIOLOGICAL RECOVERY; CONNECTIVE TISSUE CELLS; DATA; INFORMATION; KINETICS; MAMMALS; NUCLEIC ACIDS; NUMERICAL DATA; ORGANIC COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; PRIMATES; REACTION KINETICS; RECOVERY; REPAIR; SOMATIC CELLS; VERTEBRATES; 560301* - Chemicals Metabolism & Toxicology- Cells- (-1987); 550200 - Biochemistry; 016000 - Coal, Lignite, & Peat- Health & Safety

Citation Formats

Miller, J. H., and Heflich, R. H. Modeling the dose-response relationship for cytotoxicity of human cells exposed to chemical carcinogens. [N-acetoxy-2-acetylaminofluorene]. United States: N. p., 1980. Web.
Miller, J. H., & Heflich, R. H. Modeling the dose-response relationship for cytotoxicity of human cells exposed to chemical carcinogens. [N-acetoxy-2-acetylaminofluorene]. United States.
Miller, J. H., and Heflich, R. H. 1980. "Modeling the dose-response relationship for cytotoxicity of human cells exposed to chemical carcinogens. [N-acetoxy-2-acetylaminofluorene]". United States. https://www.osti.gov/servlets/purl/7056145.
@article{osti_7056145,
title = {Modeling the dose-response relationship for cytotoxicity of human cells exposed to chemical carcinogens. [N-acetoxy-2-acetylaminofluorene]},
author = {Miller, J. H. and Heflich, R. H.},
abstractNote = {Compounds like N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) result from the in vivo reduction of nitrate derivatives of benzo(..cap alpha..)pyrene. The dose-response relationship for survival of cloning ability in human fibroblasts exposed to N-AcO-AAF is being investigated to obtain a better understanding of the carcinogenic potential of coal-related air pollutants. A model is presented which correlates the survival of normal human fibroblasts after exposure to N-AcO-AAF with the rate of excision of carcinogen residues bound to DNA. The model predicts that the survival of normal cells, S/sub N/, is related to the survival of repair deficient cells, S/sub XPA/, by the equation 1n(S/sub N/) = 1n(S/sub XPA/) (1-f) where f is the fraction of potentially lethal damage repaired in the normal cell at a given dose of carcinogen. The rate of excision of AAF residues from the DNA of confluent human fibroblasts was measured over the same dose range as the survival studies. This information together with the dose-response relationship for survival of normal and repair deficient cells permits a determination of the mean number of adducts required to produce a potentially lethal lesion and the effective time available for repair. The model can be used to predict the mean lifetime of carcinogen residues on the DNA of partially repair deficient cells and the effect of recovery on the survival of normal cells. Extensions of the model to account for shoulders on the dose-response relationship curves are also discussed.},
doi = {},
url = {https://www.osti.gov/biblio/7056145}, journal = {},
number = ,
volume = ,
place = {United States},
year = {Mon Sep 01 00:00:00 EDT 1980},
month = {Mon Sep 01 00:00:00 EDT 1980}
}

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