ToxSci Advance Access published online on November 1, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp270
Cytochrome P4501A induction by 2,3,7,8-tetrachlorodibenzo-p-dioxin and two chlorinated dibenzofurans in primary hepatocyte cultures of three avian species
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* Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada, K1N 6N5
Environment Canada, National Wildlife Research Centre, Ottawa, Ontario, Canada, K1A 0H3
Michigan State University, East Lansing, Michigan, USA, 48824
University of Saskatchewan, Saskatoon, Saskatchewan, Canada, S7N 5B3
1 To whom correspondence should be addressed: Sean W. Kennedy, Environment Canada, National Wildlife Research Centre, Carleton University, 1125 Colonel By Drive, Raven Road , Ottawa, Ontario, Canada , K1A 0H3 or K1S 5B6 (courier), sean.kennedy{at}ec.gc.ca, Tel: 613-998-7384; Fax: 613-998-0458
Received September 17, 2009; revision received October 21, 2009; accepted October 26, 2009
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Abstract |
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Relative potencies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) were determined in vitro in primary hepatocyte cultures of chicken (Gallus gallus), ring-necked pheasant (Phasianus colchicus) and Japanese quail (Corturnix japonica) embryos. Concentration-dependent effects on ethoxyresorufin O-deethylase (EROD) activity, and expression of cytochrome P4501A4 and 1A5 (CYP1A4 and CYP1A5) mRNA were determined in hepatocytes exposed to serial dilutions of TCDD, PeCDF or TCDF for 24 h. In chicken hepatocytes, the three compounds were equipotent inducers of EROD activity and CYP1A4/5 mRNA expression. However, in ring-necked pheasant and Japanese quail hepatocytes, PeCDF was more potent than TCDD (3- to 5-fold in ring-necked pheasant; 13- to 30-fold in Japanese quail). Among species, the rank order of sensitivity (most to least) to EROD and CYP1A4/5 mRNA induction for TCDD and TCDF was: chicken > ring-necked pheasant > Japanese quail. In contrast, the three species were approximately equisensitive to EROD and CYP1A4/5 mRNA induction by PeCDF. It has generally been assumed that TCDD is the most potent ‘dioxin-like compound’ (DLC) and that the chicken is the most sensitive avian species to CYP1A induction by all DLCs. This study indicates that PeCDF is more potent than TCDD in ring-necked pheasant and Japanese quail hepatocytes, and that ring-necked pheasant, Japanese quail and chicken hepatocytes are equally sensitive to CYP1A induction by PeCDF.
Key Words: PCDD; PCDF; EROD; Bird; Hepatocytes; AHR.