The use of genetically engineered cells for assessing CYP2D6-related polymorphic effects.
As an example of advanced testing in the field of metabolism in an industrial environment, the introduction of some novel approaches, including the use of genetically engineered cell lines for assessing CYP 2D6-related polymorphic effects is illustrated. In this paper, it is demonstrated that novel in vitro test systems can be developed by using these genetically engineered cell lines for evaluating the potential risks associated with proprietary drugs (especially if their metabolism depends to a high extent on CYP 2D6). Moreover, it is demonstrated that, by the use of these in vitro methods, issues such as polymorphism, for which no animal models are available, can be assessed in such a way that predictions can be made on adverse effects which, up to now, could only be detected during clinical trials. Through the use of these new biotechnological in vitro metabolism models, clinically relevant data can be obtained for a scientifically-based human risk assessment, and animal use can be reduced.
Coecke
S
S
ECVAM, Institute for Health & Consumer Protection, European Commission Joint Research Centre, 21020 Ispra (VA), Italy. sandra.coecke@jrc.it
Bogni
A
A
Langezaal
I
I
Worth
A
A
Hartung
T
T
Monshouwer
M
M
D000826:Animal Testing Alternatives; D000818:Animals; D002460:Cell Line / Q000187:drug effects / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D019389:Cytochrome P-450 CYP2D6 / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism / Q000494:pharmacology; D004983:Ethanolamines / Q000378:metabolism / Q000494:pharmacology; D005818:Genetic Engineering; D006801:Humans; D008168:Lung / Q000166:cytology; D013058:Mass Spectrometry; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics*
D004983:Ethanolamines; D003915:Dextromethorphan; C010831:bufuralol; D019389:Cytochrome P-450 CYP2D6