TY - JOUR
T1 - Modulation of hepatic 2,3,7,8-TCDD cytosolic receptor levels by PCBs and organochlorine pollutants
AU - Safe, S. H.
AU - Piskorska-Pliszczynska, J.
AU - Denomme, M. A.
AU - Leece, B. D.
AU - Towner, R. A.
AU - Li, S. M.A.
N1 - Funding Information:
The financial assistance of the Natural Sciences and Engineering Research Council of Canada and the Texas Agricultural Experiment Station is gratefully acknowledged.
PY - 1986
Y1 - 1986
N2 - Administration of several persistent PCB congeners to male Wistar rats demonstrated a structure-dependent elevation of hepatic cytosolic 2,3,7,8-TCDD receptor levels. 2,2′,4,4′5,5′-Hexachlorobiphenyl and several related compounds which exhibit low affinity for the receptor protein increased receptor levels to over 300% compared to the control animals. Aroclor 1254 and 2,3,3′,4,4′,5′-hexachlorobiphenyl both bind with moderate affinity to the receptor protein (10 uM) and effect some elevation of receptor levels. In contrast, 3,3′,4,4′,5-pentachlorobiphenyl, a toxic PCB with high in vitro binding affinity (10 uM) does not alter hepatic receptor levels. Time course studies, demonstrated that 2,2′,4,4′,5,5′-hexachlorobiphenyl elevated hepatic cytosolic receptor levels for at least 14 days with the maximum elevation occurring 7 days after initial exposure to this PCB congener. In contrast, dose and time-response studies with hexachlorobenzene, several DDT analogs and heptachlor expoxide gave variable results with respect to hepatic 2,3,7,8-TCDD receptor modulation. For the PCBs, it was apparent that the most active congeners exhibited low affinity for the receptor and were phenobarbitone (PB)-like inducers of microsomal monooxygenases. Although all the organochlorine insecticides which were tested also were PB-type monooxygenase enzyme inducers only the DDT analogs modulated hepatic receptor levels.
AB - Administration of several persistent PCB congeners to male Wistar rats demonstrated a structure-dependent elevation of hepatic cytosolic 2,3,7,8-TCDD receptor levels. 2,2′,4,4′5,5′-Hexachlorobiphenyl and several related compounds which exhibit low affinity for the receptor protein increased receptor levels to over 300% compared to the control animals. Aroclor 1254 and 2,3,3′,4,4′,5′-hexachlorobiphenyl both bind with moderate affinity to the receptor protein (10 uM) and effect some elevation of receptor levels. In contrast, 3,3′,4,4′,5-pentachlorobiphenyl, a toxic PCB with high in vitro binding affinity (10 uM) does not alter hepatic receptor levels. Time course studies, demonstrated that 2,2′,4,4′,5,5′-hexachlorobiphenyl elevated hepatic cytosolic receptor levels for at least 14 days with the maximum elevation occurring 7 days after initial exposure to this PCB congener. In contrast, dose and time-response studies with hexachlorobenzene, several DDT analogs and heptachlor expoxide gave variable results with respect to hepatic 2,3,7,8-TCDD receptor modulation. For the PCBs, it was apparent that the most active congeners exhibited low affinity for the receptor and were phenobarbitone (PB)-like inducers of microsomal monooxygenases. Although all the organochlorine insecticides which were tested also were PB-type monooxygenase enzyme inducers only the DDT analogs modulated hepatic receptor levels.
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U2 - 10.1016/0045-6535(86)90519-9
DO - 10.1016/0045-6535(86)90519-9
M3 - Article
AN - SCOPUS:0022898455
VL - 15
SP - 2085
EP - 2088
JO - Chemosphere
JF - Chemosphere
SN - 0045-6535
IS - 9-12
ER -