Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in mice
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Both Aroclor 1254, a commercial polychlorinated biphenyl (PCB), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) elicit common aryl hydrocarbon (Ah) receptor-mediated effects including the induction of aryl hydrocarbon hydroxylase (AHH), a cytochrome P-450-dependent monooxygenase, the inhibition of the T-cell dependent plaque forming cells in response to sheep red blood cells (in C57BL/6 mice) and cleft palate in C57BL/6 mice. However based on ED 50 values from dose-response studies with Aroclor 1254 and 2,3,7,8-TCDD, it was apparent that the latter compound is at least 10 5 times more potent. Cotreatment of rat hepatoma H-4-II E cells or C57BL/6 mice with an ED 80-100 dose of 2,3,7,8-TCDD plus various sub-toxic (or effective) doses of Aroclor 1254 clearly shows that the commercial PCB can significantly antagonize 2,3,7,8-TCDD-mediated AHH induction (in vivo and in vitro), immunotoxicity and teratogenicity. In vitro Ah receptor binding studies suggests that Aroclor 1254 competitively inhibits the Ah receptor binding of 2,3,7,8-TCDD and this may account for the antagonist activity of the commercial PCB. © 1989.
author list (cited authors)
Safe, S., Bannister, R., Davis, D., Haake, J. M., Zacharewski, T., Mayura, K., & Phillips, T. D.