The Chemoprevention Branch of the Division of Cancer Prevention and Control at the National Cancer Institute directs a program to identify and develop drugs for human use that will prevent, delay, or reverse the progression of cellular dysplasia (e.g. intraepithelial neoplasia) to invasive cancer. Part of the drug research and development process involves preclinical toxicology studies. These studies ae performed under Good Laboratory Practices according to guidance documents published by the Food and Drug Administration and are used to support Investigational New Drug applications and eventually New Drug Applications to the FDA for the marketing approval of cancer chemopreventive agent. The contractor shall complete six batteries of aa panel of mutagenicity tests within 2 years of contract award. The compounds to-be evaluated will be specified by the NCI. The following panel of tests shall be conducted: A. GENE MUTATION IN SALMONELLA TYPHIMURIUM - The contractor shall use the standard set of strains (+S9) cited in the referenced guidelines to test for G-C and A-T base changes. Positive and negative control(s) shall be used and a rangefinding study conducted. B. MOUSE LYMPHOMA MUTATION ASSAY - The contractor shall conduct assays which measure he conversion of L5178Y cells from thymidine kinase independence to thymidine kinase dependence. C. BONE MARROW TESTS FOR DETECTION OF CLASTOGENS - The contractor shall conduct assays which measure either chromosomal aberrations in bone marrow or peripheral blood.
| Chang, Polly Y; Mirsalis, Jon; Riccio, Edward S et al. (2003) Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E. Environ Mol Mutagen 41:43-54 |
