2,2',4,4',5,5'-hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J mice
Biegel, L; Harris, M; Davis, D; Rosengren, R; Safe, L; Safe, S
HERO ID
197095
Reference Type
Journal Article
Year
1989
Language
English
PMID
| HERO ID | 197095 |
|---|---|
| In Press | No |
| Year | 1989 |
| Title | 2,2',4,4',5,5'-hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J mice |
| Authors | Biegel, L; Harris, M; Davis, D; Rosengren, R; Safe, L; Safe, S |
| Journal | Toxicology and Applied Pharmacology |
| Volume | 97 |
| Issue | 3 |
| Page Numbers | 561-71 |
| Abstract | At doses as high as 750 to 1000 mumol/kg, 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP) did not cause fetal cleft palate, suppress the splenic plaque-forming cell response to sheep red blood cells, or induce hepatic microsomal ethoxyresorufin O-deethylase (EROD) in C57BL/6J mice. Despite the lack of activity of HCBP in eliciting any of these aryl hydrocarbon (Ah) receptor-mediated responses, competitive binding studies indicated that HCBP competitively displaced 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) from the murine hepatic cytosolic receptor. Cotreatment of C57BL/6J mice with TCDD (3.7 nmol/kg) and HCBP or 4,4'-diiodo-2,2',5,5'-tetrachlorobiphenyl (I2-TCBP) (400 or 1000 mumol/kg) showed that both compounds partially antagonized TCDD-mediated cleft palate and immunotoxicity (i.e., suppression of the splenic plaque-forming cell response to sheep red blood cells), and HCBP antagonized TCDD-mediated hepatic microsomal EROD induction. Thus, HCBP and I2-TCBP, like the commercial polychlorinated biphenyl mixture Aroclor 1254, were partial antagonists of TCDD action in C57BL/6J mice; however, it was also apparent from the results that Aroclor 1254 was the more effective antagonist at lower doses. Using [3H]TCDD, it was also shown that some of the effects of HCBP on TCDD-mediated cleft palate may be due to the decreased levels of TCDD found in the fetal palates after cotreatment with TCDD and HCBP. 4,4'-[125I2]diiodo-2,2',5,5'-tetrachlorobiphenyl ([125I2]TCBP) of high specific activity (3350 Ci/mmol) was synthesized and used to investigate the direct binding of this compound to the murine hepatic Ah receptor or other cytosolic proteins. No direct specific binding was observed between 125I2-TCBP and any cytosolic proteins using a sucrose density gradient assay procedure. These results contrasted with previous studies with Aroclor 1254 that suggested that this mixture acted as a competitive Ah receptor antagonist. |
| Doi | 10.1016/0041-008x(89)90261-5 |
| Pmid | 2558429 |
| Wosid | WOS:A1989T895300019 |
| Url | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2558429 |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | N1-Mar 1N1-2,2',4,4',5,5'-hexachlorobiphenyl as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist in C57BL/6J miceN1-2558429N1-Biegel, LHarris, MDavis, DRosengren, RSafe, LSafe, SES-03843/ES/NIEHS NIH HHS/United StatesResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.Research Support, U.S. Gov't, P.H.S.United statesToxicology and applied pharmacologyToxicol Appl Pharmacol. 1989 Mar 1;97(3):561-71.N1-engAD-Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station 77843.ID-24 |
| Is Public | Yes |
| Language Text | English |
| Keyword | Animals; Antibody Formation/drug effects; Aroclors/pharmacology; Chlorodiphenyl (54% Chlorine); Cleft Palate/chemically induced; Dioxins/*antagonists & inhibitors; Enzyme Induction/drug effects; Female; Fetus/drug effects; Male; Mice; Mice, Inbred C57BL; Polychlorinated Biphenyls/*pharmacology; Pregnancy; Receptors, Aryl Hydrocarbon; Receptors, Drug/drug effects; Tetrachlorodibenzodioxin/*antagonists & inhibitors |
| Is Qa | No |