The objectives of this project are to evaluate the congener-dependency of some of the biochemical effects observed with human exposure to halogenated aromatics and the role of receptor(s) in mediating the biologic and toxic effects in placental tissue. This information will be critical in determining mechanisms of individual differences in responsiveness to the chlorinated chemicals. The metabolic activation and the role of receptor(s) in mediating the biochemical effects in human placentas are the central focus of this project. Study subjects were pregnant women identified from a registry of individuals accidentally exposed to PCBs, PCDFs, and PCQs; control subjects were age-matched to within three years of exposed subjects. Placental homogenates and microsomes from exposed subjects showed marked elevation of cytochrome P-450 monooxygenase activities when compared with samples from controls. """"""""Western blots"""""""" of placental microsomes were found to contain a protein which cross-reacted with antibody raised to rabbit cytochrome form 6, an isozyme induced by polycyclic aromatic hydrocarbons. The elevation of P-450 dependent monooxygenase showed that the biologic effects resulting from this accidental exposure (in Taiwan in 1979) can persist for at least 5 years. No relationship between the biochemical markers studied and blood PCB levels and/or clinical symptoms of exposed subjects is apparent. A consistent finding is that birth weights of offspring were lower for exposed subjects than control subjects. Work is in progress to explore the role of receptors in mediating this metabolic alteration in placentas as well as in determining the persistent PCB and PCDF congeners contributing to these biologic effects.
