Abstract: The invention provides monoclonal antibodies and other binding agents to human cytochrome P450 2D6 having advantageous properties, including capacity substantially to inhibit enzyme activity of human cytochrome P450 2D6 and lack of specific binding to other human cytochromes P450. The binding agents of the invention are useful in methods for screening drugs for metabolism by cytochrome P450 2D6, and in methods of screening individuals for a poor metabolizing human P450 2D6 phenotype.

Abstract: The invention relates to methods and compositions that are useful for detecting deficiencies in dihydropyrimidine dehydrogenase (DPD) levels in mammals including humans. Cancer patients having a DPD deficiency are at risk of a severe toxic reaction to the commonly used anticancer agent 5-fluorouracil (5-FU). Claimed are DPD genes from human and pig, methods for detecting the level of nucleic acids that encode DPD in a patient, and nucleic acids that are useful as probes for this purpose. Also claimed are methods for expressing DPD in heterologous organisms. Expression vectors that employ a DPD nucleic acid as a selectable marker are also claimed. This selectable marker functions in both prokaryotes and eukaryotes.

Abstract: Antigen binding polypeptides that specifically bind human cytochrome P450 3A3, 3A4, and 3A5 and that specifically inhibit the enzyme activity of human cytochrome P450 3A3, 3A4, and 3A5 are described. Antigen binding polypeptides that specifically bind to human cytochrome P450 3A3 and 3A4 are also described. Antigen binding polypeptides which specifically bind to human cytochrome P450 2E1 and which specifically inhibit the enzyme activity of human cytochrome P450 2E1 are described. Antigen binding polypeptides which specifically bind to human cytochrome P450 2E1 are also described. Methods of determining the contribution of human cytochrome P450s to the metabolism of compounds, using the antigen binding polypeptides of the invention, are also described.

Abstract: The invention relates to genetic material, and specifically portions of DNA, for identifying the presence or absence of a mutation in the drug metabolism gene CYP2C9 and CYP2A6. Further, the invention comprises a method for determining such mutations and a kit incorporating the genetic material of the invention for performing the said methods so as to determine the presence or absence of mutations in the drug metabolizing gene CYP2C9 and CYP2A6.

Abstract: The invention relates to methods and compositions that are useful for detecting deficiencies in dihydropyrimidine dehydrogenase (DPD) levels in mammals including humans. Cancer patients having a DPD deficiency are at risk of a severe toxic reaction to the commonly used anticancer agent 5-fluorouracil (5-FU). Claimed are DPD genes from human and pig, methods for detecting the level of nucleic acids that encode DPD in a patient, and nucleic acids that are useful as probes for this purpose. Also claimed are methods for expressing DPD in heterologous organisms. Expression vectors that employ a DPD nucleic acid as a selectable marker are also claimed. This selectable marker functions in both prokaryotes and eukaryotes.

Abstract: An improved method for measuring the activity of a promoter sequence in a mammalian cell using a reporter gene is provided. The improvement involves using a reporter cassette containing a DNA sequence encoding a cytochrome P450 with a polyadenylation signal sequence as the reporter gene. Compositions containing the cytochrome P450 reporter cassette also are provided.

Abstract: Non-tumorigenic, stable, human bronchial and liver epithelial cell lines are provided wherein the cell lines are capable of expressing human cytochrome P450 genes which have been inserted into the cell lines. Also provided are methods and kits for identifying potential mutagens, cytotoxins, carcinogens, chemotherapeutic and chemo-preventive agents utilizing these cell lines.

Abstract: A cloned cDNA encoding debrisoquine 4-hydroxylase gene and a probe for identifying humans having a genetic defect in the metabolism of a certain class of drugs of which debrisoquine is a model, have been prepared. Testing of new drugs and of humans by a simple assay has also been described.

Abstract: The present invention is related to the construction and application of vaccinia virus containing DNA sequences for encoding and efficient expression of enzymatically active cytochrome P-450 polypeptides in mammalian cells. Preparation and use of pure P1-450 and P3-450 cytochromes have been described.

Abstract: Non-tumorigenic, stable, human bronchial and liver epithelial cell lines are provided wherein the cell lines are capable of expressing human cytochrome P450 genes which have been inserted into the cell lines. Also provided are methods and kits for identifying potential mutagens, cytotoxins, carcinogens, chemotherapeutic and chemo-preventive agents utilizing these cell lines.

Abstract: Non-tumorigenic, human bronchial epithelial cell lines are provided wherein the cell lines are capable of expressing cytochrome P450 genes which have been inserted into the cell lines. Also provided are methods and kits for identifying potential mutagens, cytotoxins, carcinogens, and chemotherapeutic agents utilizing these cell lines.

Abstract: The present invention is related to the construction and application of vaccinia virus containing DNA sequences for encoding and efficient expression of enzymatically active cytochrome P-450 polypeptides in mammalian cells. Preparation and use of pure P1-450 and P3-450 cytochromes have been described.