Biochemical and molecular biological analysis of different responses to 2,3,7,8-tetrachlorodibenzo-p-dioxin in chick embryo heart and liver.
We studied the mechanism of toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the chick embryo, which is an organism highly sensitive to TCDD. TCDD was injected into egg yolks prior to embryogenesis, and eggs were incubated for 12 or 18 days. In TCDD-exposed embryos, we observed increased heart wet weight and change in the color of the liver, with abnormal fatty vesicle formation. To determine whether these effects were mediated by the aryl hydrocarbon receptor (AhR), we examined expression levels of AhR, CYP1A4, and CYP1A5. AhR was expressed continuously in the heart and liver during embryogenesis, whereas induction of CYP1A4 and CYP1A5 by TCDD was detected only in the liver. In situ hybridization study of tissue sections revealed induction of CYP1A4 in the abnormal liver tissue in which color change was not observed. To determine whether these different responses to TCDD depended on the cell type, primary cultures of chick hepatocytes and cardiac myocytes were established and 7-ethoxyresorufin-O-deethylase (EROD) activity was measured. Induction of EROD activity following exposure to TCDD was detected in hepatocytes but not in cardiac myocytes. Although the heart is a principal target organ for TCDD toxicity and AhR is expressed throughout embryogenesis, induction of CYP1A was not observed in the chick heart. Thus, we conclude that defects in the heart induced by exposure to TCDD occur via a different pathway than that occurring in the liver.
Kanzawa
Nobuyuki
N
Department of Chemistry, Faculty of Science and Technology, Sophia University, 7-1 Kioi, Chiyoda-ku, Tokyo 102-8554, Japan. n-kanza@sophia.ac.jp
Kondo
Mariko
M
Okushima
Tomoaki
T
Yamaguchi
Masatoshi
M
Temmei
Yusuke
Y
Honda
Michiyo
M
Tsuchiya
Takahide
T
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D002642:Chick Embryo; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D017931:DNA Primers; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000494:pharmacology*; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015398:Signal Transduction
D017931:DNA Primers; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1