Cell proliferation in carcinogenesis
- Univ. of Nebraska Medical Center, Omaha (USA)
Chemicals that induce cancer at high doses in animal bioassays often fail to fit the traditional characterization of genotoxins. Many of these nongenotoxic compounds (such as sodium saccharin) have in common the property that they increase cell proliferation in the target organ. A biologically based, computerized description of carcinogenesis was used to show that the increase in cell proliferation can account for the carcinogenicity of nongenotoxic compounds. The carcinogenic dose-response relationship for genotoxic chemicals (such as 2-acetylaminofluorene) was also due in part to increased cell proliferation. Mechanistic information is required for determination of the existence of a threshold for the proliferative (and carcinogenic) response of nongenotoxic chemicals and the estimation of risk for human exposure.
- OSTI ID:
- 6034720
- Journal Information:
- Science (Washington, D.C.); (USA), Vol. 249:4972; ISSN 0036-8075
- Country of Publication:
- United States
- Language:
- English
Similar Records
Mode-of-Action Uncertainty for Dual-Mode Carcinogens:Lower Bounds for Naphthalene-Induced Nasal Tumors in Rats Implied byPBPK and 2-Stage Stochastic Cancer Risk Models
Risk extrapolation for chlorinated methanes as promoters vs initiators of multistage carcinogenesis
Related Subjects
ACETYLAMINOFLUORENES
CARCINOGENESIS
TUMOR CELLS
CELL PROLIFERATION
BIOLOGICAL MODELS
DOSE-RESPONSE RELATIONSHIPS
EXPERIMENTAL NEOPLASMS
LABORATORY ANIMALS
ANIMAL CELLS
PATHOGENESIS
560300* - Chemicals Metabolism & Toxicology