Evaluation of relative potencies of PCB126 and PCB169 for the immunotoxicities in ovalbumin (OVA)-immunized mice.
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.
Pan
Xiaoqing
X
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Inouye
Kaoru
K
Ito
Tomohiro
T
Nagai
Haruko
H
Takeuchi
Yoko
Y
Miyabara
Yuichi
Y
Tohyama
Chiharu
C
Nohara
Keiko
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D005260:Female; D007107:Immune System / Q000187:drug effects*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010047:Ovalbumin / Q000276:immunology; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000633:toxicity; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D000072317:Polychlorinated Dibenzodioxins; D010047:Ovalbumin; D011078:Polychlorinated Biphenyls; D019363:Cytochrome P-450 CYP1A1; C027309:3,4,5,3',4',5'-hexachlorobiphenyl; C023035:3,4,5,3',4'-pentachlorobiphenyl