Modeling marrow damage from response data: evolution from radiation biology to benzene toxicity
| Autor: | J S Hasan, D T Jones, M D Morris |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Cell kinetics
Radiobiology Swine Differential equation Health Toxicology and Mutagenesis Biology Models Biological Colony-Forming Units Assay Lethal Dose 50 Mice Dogs Bone Marrow Animals Likelihood Functions Sheep Cell Death Dose-Response Relationship Drug Public Health Environmental and Occupational Health Data evolution Benzene Equidae Rats Kinetics Nonlinear system Nonlinear Dynamics Immunology Benzene toxicity Occupational exposure Biological system Research Article |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| DOI: | 10.1289/ehp.961041293 |
| Popis: | Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between 5 and 30 days. Mortality data from 27 experiments with 851 dose-response groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals: 12,827 mice, 2925 rats, 1676 sheep, 829 swine, 479 dogs, and 204 burros. Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal homeostasis, the dose-response data from the protracted irradiations indicate clearly that the particular lineage that is critical to hematopoietic recovery does not resemble stemlike cells with regard to radiosensitivity and repopulation rates. Instead, the weakest link in the chain of hematopoiesis was found to have an intrinsic radioresistance equal to or greater than stromal cells and to repopulate at the same rates. Model validation has been achieved by predicting the LD50 and/or fractional group mortality in 38 protracted-dose experiments (rats and mice) that were not used in fitting of model coefficients. |
| Databáze: | OpenAIRE |
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