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The Evaluation of Selected Benzodiazepine and Antihistamine Drugs in the Neonatal Mouse Tumorigenicity Bioassay and in Transgenic Human Lymphoblastoid Cells

Objective

1. To determine if the neonatal mouse bioassay can be employed to evaluate the tumorigenic potential of therapeutic drugs. 2. To examine concurrently as positive controls the genotoxic carcinogens: 4-aminobiphenyl, benzo(a)pyrene, 6-nitrochrysene, and aflatoxin B1 3. To study the metabolism and DNA adduct formation of benzodiazepine and antihistamine drugs by mouse and human liver microsomes to determine which if any cytochrome P450 is responsible for metabolic activation in mice and humans. 4. Transgenic human lymphoblastoid cell lines expressing appropriate CYP isozymes will also be employed to study the mutations and DNA binding of the subject drugs.

Investigators
Fu, Peter
Institution
DHHS/FDA - National Center for Toxicological Research
Project number
E0687901
Categories