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POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS: CORRELATION BETWEEN IN VITRO AND IN VIVO STRUCTURE ACTIVITY RELATIONSHIPS (SARS)
Citation:
Safe, S., G. Mason, B. Keys, K. Farnell, B. Zmudtka, T. Sawyer, AND e. al. POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS: CORRELATION BETWEEN IN VITRO AND IN VIVO STRUCTURE ACTIVITY RELATIONSHIPS (SARS). U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-86/535 (NTIS PB90265117), 1986.
Description:
Polychlorinated dibenzofurans (PCDFs) and dibenzo-p-dioxins (PCDDs) elicit a number of common biologic and toxic responses which are triggered by their initial binding to a cytosolic receptor protein. hese effects include the induction of several cytochrome P-448 dependent monooxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. he dose-response effects of selected PCDFs on AHH induction in rat hepatoma H-4-II E cells and cytosolic receptor binding affinities have been determined. The results of these in vivo and in vitro studies demonstrate the remarkable effects of structure on the activity of PCDFs. ystematic study of each of the four different position for chlorine substitution in the dibenzofuran ring system showed that the toxic and biologic potencies of these compounds varied with respect to differential chlorine substitution at all four position, i.e. C-3(7) > C-2(8) > C-4(6) > C-1(9). n vitro ARs for PCDDs confirmed the importance of the lateral CI substituents and also showed that 1,2 (or 6,7-) substituted PCDDs were more active than the corresponding 1,3-dichloro analogs. n addition, there were significant decreases in activity with increasing non-lateral CI substitution. he SARs for PCDFs were different from the PCDDs and this was directly related to the asymmetric structure of the former group of compounds.
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POLYCHLORINATED DIBENZO-P-DIOXINS AND DIBENZOFURANS: CORRELATION BETWEEN IN VITRO AND IN VIVO STRUCTURE ACTIVITY RELATIONSHIPS (SARS)