Preservation, induction or incorporation of metabolism into the in vitro cellular system - views to current opportunities and limitations.
Metabolism plays a major role in the toxicokinetics of a vast majority of substances, although other dispositional processes have to be considered as well. There are currently a large repertoire of primary or permanent cells/cell lines with variable metabolic capacities and a number of experimental approaches to preserve, induce or incorporate biotransformation enzymes for the development of metabolically competent cells. Many of these cell lines possess also other important dispositional characteristics mimicking the in vivo situation. Such cell models can be employed in studies targeted for estimating metabolic disposition of a substance or the production of active metabolites and ensuing toxic end points. There are also ways to collect metabolic information by using a large number of non-cellular systems and build a coherent view on metabolism, although not really replacing the actual cellular system. Early consideration of metabolic competence is a necessary prerequisite for the validation and use of cellular systems for toxicity studies and in vitro-in vivo extrapolation.
University of Oulu, Department of Pharmacology and Toxicology, P.O. Box 5000, FIN-90014 Oulu, Finland. olavi.pelkonen@oulu.fi
Olavi
O
Pelkonen
Miia
M
Turpeinen
Jukka
J
Hakkola
Khaled
K
Abass
Markku
M
Pasanen
Hannu
H
Raunio
Kirsi
K
Vähäkangas
D000826:Animal Testing Alternatives / Q000379:methods*; D006801:Humans; D010599:Pharmacokinetics; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*