January 1, 2011.
The definitive version is available at http://dx.doi.org/.
Cytochrome P450 (CYP) enzymes activate or eliminate medications and other xenobiotics, and Caffeine has been used as an indicator of activity for some CYPs. The natural genetic variation in the human population for caffeine metabolizing CYPs does not yet have an established animal model for comparison, but the natural variation in inbred mouse strains presents an attractive starting point. The project gave four different strains of mice a 40mg/kg dose of caffeine and sampled blood and liver tissue after 30 minutes. Samples were analyzed using High Performance Liquid Chromatography (HPLC), reverse transcription PCR (rtPCR), and quantitative PCR (qPCR). The DBA/2J strain showed significant evidence of relatively slower caffeine metabolism than the other strains, and the BALB/cJ strain showed some signs of faster metabolism. Quantitative comparison to mRNA expression levels will be a first step in assessing the suitability of those strains as models for slow and fast drug metabolism, with sequencing to follow.
Biochemistry | Other Animal Sciences | Systems Biology
Lawrence Livermore National Laboratory (LLNL)
This material is based upon work supported by the S.D. Bechtel, Jr. Foundation and by the National Science Foundation under Grant No. 0952013. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the S.D. Bechtel, Jr. Foundation or the National Science Foundation.