NOTE: This item is not available outside the Texas A&M University network. Texas A&M affiliated users who are off campus can access the item through NetID and password authentication or by using TAMU VPN. Non-affiliated individuals should request a copy through their local library's interlibrary loan service.
Synergistic and antagonistic effects between the halogenated aromatic hydrocarbons in C57BL/6J and DBA/2J mice
Abstract
The effects of a series of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and biphenyls (PCBs) on the hepatic microsomal enzyme inducing activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in C57BL/6J (B6) and DBA/2J (D2) mice have been investigated. Treatment of B6 mice with 2,2',4,4',5,5'-hexachlorobiphenyl (HCB, 500 umol/kg) elevated hepatic cytosolic Ah receptor levels 82-178% for up to 14 days. Scatchard analysis of [³H]-2,3,7,8-TCDD-Ah receptor binding curves confirmed that treatment with the PCB did not significantly alter receptor-radioligand affinities. In contrast, cyctosolic Ah receptor was not detectable in D2 mice tissues either in corn oil treated animals or after treatrment with the PCB (100-3000 umol/kg). Cotreatment of B6 mice with 2,2',4,4',5,5'-HCB (500 umol/kg) and 2,3,7,8-TCDD (1 nmol/kg) resulted in significant synergistic induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) compared to animals treated only with 2,3,7,8-TCDD, whereas cotreatment with maximally inducing dose levels of 2,3,7,8-TCDD (100 or 500 nmol/kg) resulted in a slight, or no, difference in the induction of AHH and EROD. In contrast, cotreatment of D2 mice with 2,2',4,4',5,5'-HCB (500 umol/kg) and 2,3,7,8-TCDD resulted in significant synergistic induction of AHH and EROD at both submaximal (80-500 nmol/kg and maximal (5000 nmol/kg) inducing dose levels of 2,3,7,8-TCDD. However when the commercial PCB mixture, Aroclor 1254, and several individual PCDDs, PCDFs and PCBs were cotreated with 2,3,7,8-TCDD, significant antagonistic effects were found on the microsomal enzyme inducing activity of 2,3,7,8-TCDD in B6 and D2 mice liver. For example, cotreatment of B6 and D2 mice with a dose of 2,3,7,8-TCDD, which submaximally induced AHH and EROD, and doses of Aroclor 1254, which elicited little or no induction activity, resulted in up to 44% and 23% antagonism of EROD induction by 2,3,7,8-TCDD in D2 and B6 liver, respectively. Cotreatment of B6 and D2 mice with a higher dose of either the antagonist or 2,3,7,8-TCDD reversed the antagonistic effects of all the compounds studied. The results show that in D2 mice much lower molar ratios of antagonist: 2,3,7,8-TCDD resulted in greater antagonism of EROD and AHH induction by 2,3,7,8-TCDD compared to B6 mice, and that within specific antagonist:agonist dose ratios, many PCDDs, PCDFs and PCBs, which competitively bind to the Ah receptor, can antagonize two Ah receptor-mediated effects of 2,3,7,8-TCDD, namely AHH induction and thymic atrophy.
Description
Typescript (photocopy).Subject
Major toxicology1987 Dissertation B219
Halocarbons
Toxicology
Drug antagonism
Drug synergism
Collections
Citation
Bannister, Roy Maxim (1987). Synergistic and antagonistic effects between the halogenated aromatic hydrocarbons in C57BL/6J and DBA/2J mice. Texas A&M University. Texas A&M University. Libraries. Available electronically from https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -26905.
Request Open Access
This item and its contents are restricted. If this is your thesis or dissertation, you can make it open-access. This will allow all visitors to view the contents of the thesis.