Toxicity testing: the search for an in vitro alternative to animal testing.
Prior to introduction to the clinic, pharmaceuticals must undergo rigorous toxicity testing to ensure their safety. Traditionally, this has been achieved using in vivo animal models. However, besides ethical reasons, there is a continual drive to reduce the number of animals used for this purpose due to concerns such as the lack of concordance seen between animal models and toxic effects in humans. Adequate testing to ensure any toxic metabolites are detected can be further complicated if the agent is administered in a prodrug form, requiring a source of cytochrome P450 enzymes for metabolism. A number of sources of metabolic enzymes have been utilised in in vitro models, including cell lines, primary human tissue and liver extracts such as S9. This review examines current and new in vitro models for toxicity testing, including a new model developed within the authors' laboratory utilising HepG2 liver spheroids within a co-culture system to examine the effects of chemotherapeutic agents on other cell types.
Centre for Research in Biomedicine, Faculty of Health and Life Sciences, University of the West of England, Coldharbour Lane, Frenchay, Bristol BS16 1QY, UK. jennifer2.may@uwe.ac.uk
J E
JE
May
J
J
Xu
H R
HR
Morse
N D
ND
Avent
C
C
Donaldson
D000293:Adolescent; D000368:Aged; D000826:Animal Testing Alternatives / Q000379:methods* / Q000639:trends; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000639:trends; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000166:cytology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects; D051379:Mice; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology / Q000592:standards; D051381:Rats; D013045:Species Specificity; D018874:Spheroids, Cellular; D018675:Toxicity Tests / Q000379:methods*
D004364:Pharmaceutical Preparations; D011355:Prodrugs; D003577:Cytochrome P-450 Enzyme System