The induction of DNA damage and the resulting sequelae of mutations and chromosomal rearrangements are primary mechanisms by which cancers arise. DNA damage has also been implicated in arteriosclerosis and certain birth defects. Thus, there is an important need for sensitive methods for identifying compounds that mutate or otherwise damage DNA. The very high cost of long-term animal studies dictates that short- and medium-term mutagenicity assays must be relied on to eliminate potentially hazardous chemicals from development, and to prioritize chemicals for further study. Furthermore, as new chemicals and therapeutic drugs are being developed ever more rapidly, the need for short-term tests with high throughput capabilities increases.
The aim of this Phase II research effort is to refine, standardize, and validate an automated system for scoring chromosome damage in cultured mammalian cells. Specifically, a flow cytometric method for enumerating genotoxicant-induced micronuclei will be developed and vigorously tested. This system will be extremely valuable as an early screening test for identifying genotoxicants, and is expected to prove particularly valuable to the Chemical Manufacturing and Pharmaceutical Industries which are required to assess compounds' DNA-damaging potential. The automated scoring systems' commercial potential will be realized through: 1) fee-for-service contract testing, and 2) bundling dyes and other reagents required to perform these analyses into commercially available kits.
| Avlasevich, Svetlana L; Bryce, Steven M; Cairns, Sian E et al. (2006) In vitro micronucleus scoring by flow cytometry: differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability. Environ Mol Mutagen 47:56-66 |
