Test system comprising cells expressing different cytochrome P450 2D6 alleles used to investigate genetically caused metabolite toxicity and to determine toxic, mutagenic or carcinogenic effect of compounds

摘要

Test system comprising cells expressing a cytochrome P450 2D6 (hCYP2D6) allele heterolog, and at least three P450 2D6 alleles are expressed in the system, is new. Independent claims are also included for the following: (1) screening for substances metabolized by human cytochrome P450 2D6, comprising contacting cells of the test system with a substance and measuring metabolite products; (2) determining new P450 2D6 alleles, comprising heterologous expression of the allele in question in a cell and comparing P450 2D6-dependent metabolism in this cell with cells of the test system; and (3) quantifying cytochrome P450 content, comprising solubilizing P450 cytochromes with a non-ionizing detergent Emulgen 913, centrifugation and measurement by CO difference spectra.