| Budget Amount *help |
¥4,110,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
The objective of this research is to investigate the potential sensitivity of avian species to dioxins and its related compounds and to evaluate the risk to these chemicals by characterizing the avian AHR isoforms (AHR1 and AHR2). Our previous study demonstrated that avian species possesses two distinct aryl hydrocarbon receptors (AHR1 and AHR2). Initially, to clarify the molecular mechanism of avian AHR-CYP1A signaling pathway,2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding affinities and TCDD-induced transcriptional activities of AHR isoforms from chicken, black-footed albatross, common cormorant and jungle crow were investigated. All avian AHR isoforms exhibited specific binding affinity to [^3H]TCDD, as assessed by velocity sedimentation. An in vitro reporter gene assay revealed that EC_<50>for cormorant cytochrome P450(CYP)1A5 transactivation by cormorant AHR1 following TCDD treatment was 10-fold greater than that of chicken CYP1A5 by chicken AHR1, suggesting that cormorant may
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be 10-fold resistant to TCDD compared to chicken. Intriguingly, the TCDD-EC_<50>for chicken and cormorant CYP1A5 promoters was similar irrespective of the species of AHR1, indicating that the structure of AHR, rather than that of CYP1A5 promoter, may contribute to the transactivation. AHR2s from chicken, albatross and cormorant had reduced transcriptional efficiencies to TCDD as compared to AHR1s from the corresponding species. In contrast, the transcriptional ability of crow AHR2 was comparable to that of AHR1, implying the interspecies difference in transactivation potential of avian AHR2 isoforms.
Tissue expression profiles of AHR isoform mRNAs in cormorant and crow revealed that AHR1s were expressed in most tissues, whereas AHR2s were detectable in limited tissues. Comparison of hepatic mRNA expression levels of two AHR isoforms showed a species difference ; AHR1 is dominant than AHR2 in cormorant, but AHR2 is the major form in the crow. These results suggest that function of AHR isoforms mediating the response to DRC exposure is diversified even within avian species. Less
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