TY - JOUR
T1 - Polychlorinated dibenzo-p-dioxins and dibenzofurans
T2 - Correlation between in vitro and in vivo structure-activity relationships (SARs)
AU - Safe, S.
AU - Mason, G.
AU - Keys, B.
AU - Farrell, K.
AU - Zmudzka, B.
AU - Sawyer, T.
AU - Piskorska-Pliszczynska, J.
AU - Safe, L.
AU - Romkes, M.
AU - Bandiera, S.
N1 - Funding Information:
This research was supported by U.S. Environmental Protection Agency, the Texas Agricultural Experiment Station and Natural Sciences and Engineering Research Council of Canada.
PY - 1986
Y1 - 1986
N2 - 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. These effects include the induction of several cytochrome P-448 dependent monooxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. The 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. A systematic 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). In vitro SARs 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. In addition, there were significant decreases in activity with increasing non-lateral CI substitution. The SARs for PCDFs were different from the PCDDs and this was directly related to the asymmetric structure of the former group of compounds.
AB - 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. These effects include the induction of several cytochrome P-448 dependent monooxygenases (eg, aryl hydrocarbon hydroxylase, AHH), body weight loss and thymic atrophy. The 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. A systematic 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). In vitro SARs 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. In addition, there were significant decreases in activity with increasing non-lateral CI substitution. The 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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U2 - 10.1016/0045-6535(86)90460-1
DO - 10.1016/0045-6535(86)90460-1
M3 - Article
AN - SCOPUS:0022918457
VL - 15
SP - 1725
EP - 1731
JO - Chemosphere
JF - Chemosphere
SN - 0045-6535
IS - 9-12
ER -