Abstract
| Grant Number: | 5R44CA113243-03 |
| Project Title: | Flow cytometry-based Unscheduled DNA Synthesis (FLUDS) |
| PI Information: | Name | Email | Title |
| DEGEORGE, GEORGE |
mbres@enter.net |
DIRECTOR OF TOXICOLOGY |
Abstract:
DESCRIPTION (provided by applicant): There is a growing need in industry for an inexpensive screening assay which can reliably determine the genotoxic potential of the large number of new chemical compounds synthesized each year. The Unscheduled DNA Synthesis (UDS) Assay is a proven method to identify and characterize genotoxic chemicals. However, several technical aspects of the standard assay limit its widespread use. We have made modifications to the standard UDS assay in Phase I studies through incorporation of flow cytometry as a detection method, and have proven feasibility of our optimized version of UDS, termed FLUDS. The FLUDS assay allows higher throughput and much shorter study times (a few days versus weeks for the standard UDS). This new assay can discriminate between innate and biotransformed genotoxicants, and is fully quantitative. It has reliably predicted the UDS induced by ethylnitrosourea, aphidicolin, 2- acetylaminofluorene, and fluorene. We intend to pre-validate the FLUDS assay by testing an expanded set of genotoxic and non-genotoxic chemicals in preparation for a multi-laboratory validation under ICCVAM guidelines. The pre-validated FLUDS assay would be of considerable commercial value to customers in the pharmaceutical, chemical, cosmetic and consumer products industries.
Thesaurus Terms:
DNA damage, DNA replication, flow cytometry, mutagen testing, nucleic acid biosynthesis, technology /technique development, toxicant screening
high throughput technology
cell line, chick embryo
| Institution: | MB RESEARCH LABORATORIES, INC. |
| PO BOX 178 |
| SPINNERSTOWN, PA 18968 |
| Fiscal Year: | 2005 |
| Department: | |
| Project Start: | 15-SEP-2004 |
| Project End: | 31-AUG-2008 |
| ICD: | NATIONAL CANCER INSTITUTE |
| IRG: | ZRG1 |
|
