An objective of the National Toxicology Program is to conduct chemical toxicity studies to determine the potential for toxicity in humans. One toxicity endpoint that is of concern to the NTP is the induction of heritable mutations in germ cells with the resulting risk of newly arisen genetic disease. The NTP test efforts sponsored by the Cellular and Genetic Toxicology Branch constitute the largest program in the country to identify and characterize chemicals that induce genetic damage in the germ cells of exposed mammals. This contract to combine other genetic endpoints with the mouse electrophoretic germinal mutation assay will be an integral part of the Cellular and Genetic Toxicology Branch's program in mammalian germ cell mutagenesis testing. The general objectives of this study are three-fold: 1. To expand the mouse electrophoretic germinal mutation test to include additional endpoints. Among the endpoints proposed for addition are the morphological/visible characteristics affected by specific genes, morphological characteristics not associated with specific genes, dominant cataract mutations, heritable translocations and molecular alterations identifiable by analysis of specific DNA sequences with sequence-specific probes after cleavage with restriction enzymes and electrophoretic separation (Southern Blotting). 2. To demonstrate the utility of this expanded test system using a model germ cell mutagen to be specified by the Project Officer. Mutagenicity tests will be conducted with treated males and with treated females. 3. To use this expanded test system, to test two compounds which are known mutagens but whose mutagenicity in mammalian germ cells is unknown.
| Barnett, Lois B; Lewis, Susan E (2003) Chlornaphazine and chlorambucil induce dominant lethal mutations in male mice. Mutat Res 543:145-54 |
| Shelby, M D; Bishop, J B; Mason, J M et al. (1993) Fertility, reproduction, and genetic disease: studies on the mutagenic effects of environmental agents on mammalian germ cells. Environ Health Perspect 100:283-91 |
| Peters, J; Lewis, S E (1991) Electrophoretic variation in multiple recessive tester, T, stock mice. Mutat Res 249:323-30 |
