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

Conference · Mon Sep 01 00:00:00 EDT 1980

OSTI ID:7056145

Miller, J. H.; Heflich, R. H.

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.

• Research Organization: Battelle Pacific Northwest Labs., Richland, WA (USA); National Center for Toxicological Research, Jefferson, AR (USA)
• DOE Contract Number: AC06-76RL01830
• OSTI ID: 7056145
• Report Number(s): PNL-SA-8679; CONF-801039-5
• Resource Relation: Conference: 20. annual Hanford Life Sciences symposium, Richland, WA, USA, 19 Oct 1980
• Country of Publication: United States
• Language: English

Related Subjects

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