Project Summary (1995-2000)

A dose response study of the teratogenic potential of chlorinated hydrocarbons is being continued and identification/examination of several molecular markers as indicators of cardiac teratogenesis is being pursued in this study. Several molecules, known to be critical for normal heart development, are being examined in animals or cardiac cell cultures exposed to chlorinated hydrocarbons to determine whether regulation of gene expression is affected during cardiogenesis. Further, comparative gene amplification (differential display polymerase chain reaction), is being used to identify other genes that are specifically perturbed by exposure to chlorinated hydrocarbons. Once indicator molecules have been identified, there will be several significant advantages to this molecular approach. Each marker probe can be used for dose-sensitivity studies to identify critical threshold levels of exposure to the teratogens. Comparison between different strains of experimental animals can be used to address differences in sensitivity to teratogens in different genetic backgrounds. These probes can also be used in studies of normal heart development. Probes that prove to be reliable indicators of teratogen exposure can be used to identify the human homologue of these genes and may eventually be used as indicators in exposed human populations. Such probes may also be used to assess the effects of various remediation protocols.