The sister chromatid exchange (SCE) technique has been proposed as a mutagenic assay in genetic toxicology testing. The complete and successful application of this procedure is currently not possible because the underlying mechanism(s) and biological consequences of SCE are not known. We propose to use the chick embryo to study the nature of mutagen-induced SCE and the effects of such in the hemopoietic and immune systems at pre- and post-natal stages. In addition, this research contributes to the development of an in vivo assay for detecting mutagens and their long-range effects resulting from prenatal exposure. Chick embryos will be exposed to selected mutagen/non-mutagen pairs to determine the specificity of the SCE response and its use in discriminating weak from strong mutagens. Chick embryos at early and late developmental ages will be exposed to direct and indirect-acting chemical mutagens to test the hypothesis that with the progressive growth and differentiation of tissues the extent of metabolic toxification/detoxification increases. Thus, the extent of mutagenesis by promutagens increases while the reverse is true for direct-acting mutagens. The protocol of exposing embryos at different ages to promutagens will also be used for the assay of effects on differentiation and functioning of white and red blood cells. Growth rate, immune functioning, and production of tumors will be studied in chickens surviving the prenatal exposure to mutagen/non-mutagen pairs. The frequency of SCE induced by the chemicals will be studied in parallel embryos injected with BrdU for labeling chromosomal DNA. The degree and type of malformations induced following prenatal exposure will be correlated with the frequency of SCE. If SCE is a manifestation of damage to the DNA that leads to point mutations, we expect to see some deleterious phenotypic effects particularly if the level of SCE is high in every cell. Our research also contributes to knowledge of the action of flame retardants, mycotoxins, and dyes in a developing system.
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