TY - JOUR
T1 - Evaluation of relative potencies of PCB126 and PCB169 for the immunotoxicities in ovalbumin (OVA)-immunized mice
AU - Pan, Xiaoqing
AU - Inouye, Kaoru
AU - Ito, Tomohiro
AU - Nagai, Haruko
AU - Takeuchi, Yoko
AU - Miyabara, Yuichi
AU - Tohyama, Chiharu
AU - Nohara, Keiko
N1 - Funding Information:
The authors wish to thank Dr. J. Yonemoto, Dr. H. Fuijmaki (NIES) and Dr. M. Kubo (Science University of Tokyo) for their helpful discussions, M. Matsumoto for her technical assistance and K. Nakazawa for her secretarial assistance. This work was supported in part by grants from CREST, JST, the Ministry of Health, Labor and Welfare (C.T.), and the Ministiry of the Environment.
PY - 2004/11/1
Y1 - 2004/11/1
N2 - Dioxin-like polychlorinated biphenyls (PCBs) exert their toxicities by activating the arylhydrocarbon receptor (AhR), a ligand-dependent transcription factor, in a similar manner to the most toxic dioxin, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD). In the present study, we re-evaluated the relative potency (REP) of the toxic members of dioxin-like PCBs, PCB126 (toxic equivalency factor, TEF 0.1) and PCB169 (TEF 0.01) relative to TCDD, focusing our attention on their effects on the immune reactions of mice immunized with ovalbumin (OVA). Thymus involution, IgM production, and IL-5 produced by the splenocytes were examined in addition to CYP1A1 induction, the established index of AhR-activation, in the spleen. PCB126 had an REP value of 0.1 because of its effects on thymus, IgM, IL-5, and CYP1A1 induction in the spleen, although its effect on IgG1 production was weaker. On the other hand, PCB169 had a smaller REP value estimated at less than 0.01 with regard to CYP1A1 induction in the spleen and all examined immunological effects, except for IgM production. The tissue concentrations of PCB169 and TCDD could not explain the reason for the smaller potency of PCB169, since the spleen contained a higher proportion of PCB169 to TCDD than dosed. These results indicate that dioxin-like PCBs, especially PCB169, shows deviating REPs against immune reactions, and also suggest that PCB169-liganded AhR behaves differently from TCDD-liganded AhR in immune cells.
AB - Dioxin-like polychlorinated biphenyls (PCBs) exert their toxicities by activating the arylhydrocarbon receptor (AhR), a ligand-dependent transcription factor, in a similar manner to the most toxic dioxin, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD). In the present study, we re-evaluated the relative potency (REP) of the toxic members of dioxin-like PCBs, PCB126 (toxic equivalency factor, TEF 0.1) and PCB169 (TEF 0.01) relative to TCDD, focusing our attention on their effects on the immune reactions of mice immunized with ovalbumin (OVA). Thymus involution, IgM production, and IL-5 produced by the splenocytes were examined in addition to CYP1A1 induction, the established index of AhR-activation, in the spleen. PCB126 had an REP value of 0.1 because of its effects on thymus, IgM, IL-5, and CYP1A1 induction in the spleen, although its effect on IgG1 production was weaker. On the other hand, PCB169 had a smaller REP value estimated at less than 0.01 with regard to CYP1A1 induction in the spleen and all examined immunological effects, except for IgM production. The tissue concentrations of PCB169 and TCDD could not explain the reason for the smaller potency of PCB169, since the spleen contained a higher proportion of PCB169 to TCDD than dosed. These results indicate that dioxin-like PCBs, especially PCB169, shows deviating REPs against immune reactions, and also suggest that PCB169-liganded AhR behaves differently from TCDD-liganded AhR in immune cells.
KW - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
KW - Immunotoxicity
KW - PCB126
KW - PCB169
KW - Toxic equivalency factor (TEF)
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U2 - 10.1016/j.tox.2004.06.024
DO - 10.1016/j.tox.2004.06.024
M3 - Article
C2 - 15369848
AN - SCOPUS:5144227384
SN - 0300-483X
VL - 204
SP - 51
EP - 60
JO - Toxicology
JF - Toxicology
IS - 1
ER -