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1.
Comp Biochem Physiol C Toxicol Pharmacol ; 155(3): 498-505, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22227438

ABSTRACT

Primary cultures of ring-necked pheasant (Phasianus colchicus) and Japanese quail (Coturnix japonica) embryo hepatocytes were used to compare the potencies of highly purified hexachlorobenzne (HCB-P), reagent-grade HCB (RG-HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as inducers of ethoxyresorufin O-deethylase (EROD) activity, cytochrome P4501A (CYP1A4) messenger ribonucleic acid (mRNA) and CYP1A5 mRNA. HCB-P, RG-HCB and TCDD all induced EROD activity and up-regulated CYP1A4 and CYP1A5 mRNA. Induction was not caused by contamination of HCB with polychlorinated dibenzo-p-dioxins, dibenzofurans or biphenyls. Based upon a comparison of the EC(50) and EC(threshold) values for EROD and CYP1A4/5 concentration-response curves, the potency of HCB relative to TCDD was 0.001 in ring-necked pheasant and 0.01 in Japanese quail embryo hepatocytes. Differences in species sensitivity to HCB were found to be mainly dictated by differences in species sensitivity to TCDD rather than differences in the absolute potency of HCB. Consequently, ring-necked pheasant and Japanese quail embryo hepatocytes were found to be equally sensitive to HCB exposure. Species sensitivity comparisons were also made with chicken (Gallus gallus domesticus) and revealed that chicken embryo hepatocytes were less responsive to EROD induction (lower maximal response) by HCB compared to the embryo hepatocytes of pheasant and quail.


Subject(s)
Aryl Hydrocarbon Hydroxylases/metabolism , Coturnix/metabolism , Galliformes/metabolism , Gene Expression Regulation, Enzymologic , Hepatocytes/drug effects , Hexachlorobenzene/toxicity , Animals , Aryl Hydrocarbon Hydroxylases/genetics , Cell Survival , Coturnix/embryology , Coturnix/genetics , Embryo, Nonmammalian/cytology , Enzyme Activation , Enzyme Induction , Galliformes/embryology , Galliformes/genetics , Hepatocytes/cytology , Hepatocytes/enzymology , Polychlorinated Dibenzodioxins/toxicity , Primary Cell Culture , RNA, Messenger/genetics , RNA, Messenger/metabolism , Species Specificity
2.
Toxicol Appl Pharmacol ; 248(3): 185-93, 2010 Nov 01.
Article in English | MEDLINE | ID: mdl-20682327

ABSTRACT

Some uncertainty exists regarding the purity of hexachlorobenzene (HCB) used in past toxicity studies. It has been suggested that reported toxic and biochemical effects initially attributed to HCB exposure may have actually been elicited by contamination of HCB by polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). Herein, primary cultures of chicken embryo hepatocytes (CEH) were used to compare the potencies of two lots of reagent-grade hexachlorobenzene (HCB-old [HCB-O] and HCB-new [HCB-N]), highly purified HCB (HCB-P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as inducers of ethoxyresorufin O-deethylase (EROD) activity, cytochrome P4501A4 (CYP1A4) messenger ribonucleic acid (mRNA) and CYP1A5 mRNA. The study also compared the EROD- and CYP1A4/5 mRNA-inducing potencies of HCB to the potencies of two mono-ortho substituted polychlorinated biphenyls (PCBs), 2,3,3',4,4'-pentachlorobiphenyl (PCB 105) and 2,3'4,4',5-pentachlorobiphenyl (PCB 118). HCB-O, HCB-N and HCB-P all induced EROD activity and up-regulated CYP1A4 and CYP1A5 mRNAs. Induction was not caused by contamination of HCB with PCDDs or PCDFs. Based upon a comparison of the EC(50) and EC(threshold) values for EROD and CYP1A4/5 mRNA concentration-response curves, the potency of HCB relative to the potency of TCDD was 0.0001, and was similar to that of PCB 105 and PCB 118. The maximal EROD activity and CYP1A4/5 mRNA expression differed greatly between HCB and TCDD, and may contribute to an overestimation of the ReP value calculated for highly purified HCB.


Subject(s)
Cytochrome P-450 CYP1A1/biosynthesis , Drug Contamination , Hepatocytes/drug effects , Hexachlorobenzene/isolation & purification , Hexachlorobenzene/toxicity , Animals , Aryl Hydrocarbon Hydroxylases/biosynthesis , Cells, Cultured , Chick Embryo , Dose-Response Relationship, Drug , Drug Contamination/prevention & control , Enzyme Induction/drug effects , Enzyme Induction/genetics , Hepatocytes/enzymology
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