Cytochrome P4501A induction by dioxin-like compounds in avian hepatocyte cultures

Abstract

In this study, the potencies of 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF) and 2,3,7,8-tetrachlorodibenzofuran (TCDF) to induce cytochrome P4501A (CYP1A) were determined. The concentration-dependent effects of TCDD, PeCDF and TCDF on ethoxyresorufin O-deethylase (EROD) activity, CYP1A4 mRNA and CYP1A5 mRNA expression were measured in primary hepatocyte cultures of chicken (Gallus gallus), ring-necked pheasant (Phasianus colchicus), Japanese quail (Corturnix japonica ), and herring gull (Larus argentatus) embryos exposed for 24h. The results demonstrated that PeCDF was as potent as TCDD to induce CYP1A in chicken hepatocytes, but that PeCDF was more potent than TCDD in ring-necked pheasant, Japanese quail and herring gull hepatocytes. Moreover, the chicken was the most sensitive species to CYP1A induction by TCDD or TCDF, but all species were approximately equisensitive to CYP1A induction by PeCDF. Together these results showed that all species do not respond the same way to different DLCs, suggesting that interactions between a DLC and a species are structure- and cell type-dependent. These results raise interesting questions concerning the molecular mechanism of action of DLCs and the toxic equivalency factors that are broadly assigned to all avian species.