PloS one, 2011-08, Vol.6 (8), p.e23128
2011
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- Autor(en) / Beteiligte
- Titel
- A method for efficient calculation of diffusion and reactions of lipophilic compounds in complex cell geometry
- Ist Teil von
- PloS one, 2011-08, Vol.6 (8), p.e23128
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- A general description of effects of toxic compounds in mammalian cells is facing several problems. Firstly, most toxic compounds are hydrophobic and partition phenomena strongly influence their behaviour. Secondly, cells display considerable heterogeneity regarding the presence, activity and distribution of enzymes participating in the metabolism of foreign compounds i.e. bioactivation/biotransformation. Thirdly, cellular architecture varies greatly. Taken together, complexity at several levels has to be addressed to arrive at efficient in silico modelling based on physicochemical properties, metabolic preferences and cell characteristics. In order to understand the cellular behaviour of toxic foreign compounds we have developed a mathematical model that addresses these issues. In order to make the system numerically treatable, methods motivated by homogenization techniques have been applied. These tools reduce the complexity of mathematical models of cell dynamics considerably thus allowing to solve efficiently the partial differential equations in the model numerically on a personal computer. Compared to a compartment model with well-stirred compartments, our model affords a more realistic representation. Numerical results concerning metabolism and chemical solvolysis of a polycyclic aromatic hydrocarbon carcinogen show good agreement with results from measurements in V79 cell culture. The model can easily be extended and refined to include more reactants, and/or more complex reaction chains, enzyme distribution etc, and is therefore suitable for modelling cellular metabolism involving membrane partitioning also at higher levels of complexity.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0023128Titel-ID: cdi_plos_journals_1307923110
- Format
- –
- Schlagworte
- 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - chemistry, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - metabolism, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - toxicity, ACTIVATION, Analysis, Animals, Aromatic hydrocarbons, Biocompatibility, Biological Transport, Biology, Biotransformation, BREAST-CANCER CELLS, Carcinogens, Carcinogens, Environmental - chemistry, Carcinogens, Environmental - metabolism, Carcinogens, Environmental - toxicity, Cell culture, Cell Line, Cell Membrane - drug effects, Cell Membrane - metabolism, Cells, Cells (Biology), Complexity, Computational chemistry, Computer Science, Computer simulation, CONJUGATION, Cytoplasm, Deoxyribonucleic acid, Differential equations, Diffusion, DNA, DNA Adducts - drug effects, ELECTRON-MICROSCOPY, Environmental health, Enzymes, Experiments, GLUTATHIONE TRANSFERASES, Humans, Hydrophobic and Hydrophilic Interactions, Hydrophobicity, Intracellular Space - drug effects, Intracellular Space - metabolism, Laboratories, Lipids, Lipophilic, Mammalian cells, Mathematical analysis, Mathematical models, Mathematics, Medical research, Medicin och hälsovetenskap, MEMBRANES, METABOLISM, Metabolites, Methods, Microscopy, Models, Biological, Multimedia, Numerical methods, Organic chemicals, Partial differential equations, Physicochemical properties, Physiological aspects, Pollutants, POLYCYCLIC AROMATIC-HYDROCARBONS, REGION DIOL EPOXIDES, Solvolysis, TOPOTECAN, Toxicity Tests - methods, Trends