Simulating microdosimetry in a virtual hepatic lobule.

The liver plays a key role in removing harmful chemicals from the body and is therefore often the first tissue to suffer potentially adverse consequences. To protect public health it is necessary to quantitatively estimate the risk of long-term low dose exposure to environmental pollutants. Animal t...

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Autores principales:	John Wambaugh, Imran Shah
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/9533a02ee2f7487e95351188b9e05c9d
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spelling	oai:doaj.org-article:9533a02ee2f7487e95351188b9e05c9d2021-11-25T05:42:32ZSimulating microdosimetry in a virtual hepatic lobule.1553-734X1553-735810.1371/journal.pcbi.1000756https://doaj.org/article/9533a02ee2f7487e95351188b9e05c9d2010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20421935/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The liver plays a key role in removing harmful chemicals from the body and is therefore often the first tissue to suffer potentially adverse consequences. To protect public health it is necessary to quantitatively estimate the risk of long-term low dose exposure to environmental pollutants. Animal testing is the primary tool for extrapolating human risk but it is fraught with uncertainty, necessitating novel alternative approaches. Our goal is to integrate in vitro liver experiments with agent-based cellular models to simulate a spatially extended hepatic lobule. Here we describe a graphical model of the sinusoidal network that efficiently simulates portal to centrilobular mass transfer in the hepatic lobule. We analyzed the effects of vascular topology and metabolism on the cell-level distribution following oral exposure to chemicals. The spatial distribution of metabolically inactive chemicals was similar across different vascular networks and a baseline well-mixed compartment. When chemicals were rapidly metabolized, concentration heterogeneity of the parent compound increased across the vascular network. As a result, our spatially extended lobule generated greater variability in dose-dependent cellular responses, in this case apoptosis, than were observed in the classical well-mixed liver or in a parallel tubes model. The mass-balanced graphical approach to modeling the hepatic lobule is computationally efficient for simulating long-term exposure, modular for incorporating complex cellular interactions, and flexible for dealing with evolving tissues.John WambaughImran ShahPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 6, Iss 4, p e1000756 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 John Wambaugh Imran Shah Simulating microdosimetry in a virtual hepatic lobule.
description	The liver plays a key role in removing harmful chemicals from the body and is therefore often the first tissue to suffer potentially adverse consequences. To protect public health it is necessary to quantitatively estimate the risk of long-term low dose exposure to environmental pollutants. Animal testing is the primary tool for extrapolating human risk but it is fraught with uncertainty, necessitating novel alternative approaches. Our goal is to integrate in vitro liver experiments with agent-based cellular models to simulate a spatially extended hepatic lobule. Here we describe a graphical model of the sinusoidal network that efficiently simulates portal to centrilobular mass transfer in the hepatic lobule. We analyzed the effects of vascular topology and metabolism on the cell-level distribution following oral exposure to chemicals. The spatial distribution of metabolically inactive chemicals was similar across different vascular networks and a baseline well-mixed compartment. When chemicals were rapidly metabolized, concentration heterogeneity of the parent compound increased across the vascular network. As a result, our spatially extended lobule generated greater variability in dose-dependent cellular responses, in this case apoptosis, than were observed in the classical well-mixed liver or in a parallel tubes model. The mass-balanced graphical approach to modeling the hepatic lobule is computationally efficient for simulating long-term exposure, modular for incorporating complex cellular interactions, and flexible for dealing with evolving tissues.
format	article
author	John Wambaugh Imran Shah
author_facet	John Wambaugh Imran Shah
author_sort	John Wambaugh
title	Simulating microdosimetry in a virtual hepatic lobule.
title_short	Simulating microdosimetry in a virtual hepatic lobule.
title_full	Simulating microdosimetry in a virtual hepatic lobule.
title_fullStr	Simulating microdosimetry in a virtual hepatic lobule.
title_full_unstemmed	Simulating microdosimetry in a virtual hepatic lobule.
title_sort	simulating microdosimetry in a virtual hepatic lobule.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/9533a02ee2f7487e95351188b9e05c9d
work_keys_str_mv	AT johnwambaugh simulatingmicrodosimetryinavirtualhepaticlobule AT imranshah simulatingmicrodosimetryinavirtualhepaticlobule
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Simulating microdosimetry in a virtual hepatic lobule.

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