PCL102H1 Lecture Notes - Lecture 17: Hepatotoxicity, Serum (Blood), Metabolomics
Drugs often fail in late-stage clinical trials due to unpredicted adverse effects. Identifying and characterizing dose-limiting toxicity of companies" lead compounds before they are tested in clinical trials is essential part of drug development. Whether drug or chemical poses sufficiently low risk to be marketed for stated purpose. Liver enzymes in serum (blood) as index of liver toxicity. Reduction using fewer animals, maxing amount of info per animal. Refinement alternatives animal housing and environment (toys); minimize distress, pain. Ames test method that uses bacteria to test whether a given chemical can cause mutations in dna. Use salmonella strain with mutations in genes involved in histidine synthesis require histidine for growth, but can"t make it. Tests ability of chemical to cause mutations that allow bacteria to create own histidine. Bacteria spread on plate with small amount of histidine. When histidine is depleted, only bacteria that have gained ability to produce own histidine will survive.