Highly purified hexachlorobenzene induces cytochrome P4501A in primary cultures of chicken embryo hepatocytes

Journal Article · Mon Nov 01 00:00:00 EDT 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.07.022· OSTI ID:21460225

Mundy, Lukas J ^[1]; Jones, Stephanie P; Crump, Doug; Herve, Jessica C ^[2]; Konstantinov, Alex; Utley, Fiona; Potter, David ^[3]

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1. Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario (Canada)
2. Environment Canada, National Wildlife Research Centre, Ottawa, Ontario (Canada)
3. Wellington Laboratories Inc., Research Division, Guelph, Ontario (Canada)

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{sub 50} and EC{sub 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.

• OSTI ID: 21460225
• Journal Information: Toxicology and Applied Pharmacology, Vol. 248, Issue 3; Other Information: DOI: 10.1016/j.taap.2010.07.022; PII: S0041-008X(10)00260-7; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CHICKENS
DIOXIN
EMBRYOS
FURANS
LIVER CELLS
MESSENGER-RNA
POLYCHLORINATED BIPHENYLS
TOXICITY
ANIMAL CELLS
ANIMALS
AROMATICS
BIRDS
CHLORINATED AROMATIC HYDROCARBONS
FOWL
HALOGENATED AROMATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
NUCLEIC ACIDS
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
RNA
SOMATIC CELLS
VERTEBRATES