The long term objective is to validate the fetal mouse salivary gland culture system as an in vitro assay system for detecting chemical teratogens. This may help in preventing future birth defects.
The specific aims are: 1. to determine the concentration of a chemical that will reduce growth by 50%, 2. to compare this concentration to the in vivo concentration reported as the lowest teratogenic dose, 3. to test this system as a complement to other in vitro systems by selecting chemicals reported as false negatives or false positives in these systems and to test the range of this system by selecting chemicals that represent different modes of action. Salivary glands from 13 day mouse fetuses will be removed and placed in an untreated control or in one of 3 concentrations of the test chemical. A total of 20 glands will be included in each treatment. Growth will be determined by calculating a ratio of the number of lobes present after 48 hours in culture by the number of lobes present at explantation. The means of these ratios will be used to construct dose response curves. By extrapolation, the concentration that reduces lobe production by 50% will be determined and this value will be compared to the lowest teratogenic dose reported in the literature.
Lyng, R D; Scalf, R; Monteith, D (1991) Metabolic activation in the fetal mouse salivary gland culture system with rat hepatocytes, rat S-9, and human S-9. Teratog Carcinog Mutagen 11:31-9 |
Lyng, R D (1990) Use of fetal mouse salivary glands in culture to detect embryotoxicity: evaluation of eight additional chemicals. Toxicol Lett 54:245-51 |
Lyng, R D (1989) Test of six chemicals for embryotoxicity using fetal mouse salivary glands in culture. Teratology 39:591-9 |