IMMUNOTOXIC POTENCIES OF POLYCHLORINATED BIPHENYL (PCB), DIBENZOFURAN (PCDF) AND DIBENZO-P-DIOXIN (PCDD) CONGENERS IN C57BL/6 AND DBA/2 MICE

被引:49
作者
HARPER, N [1 ]
CONNOR, K [1 ]
SAFE, S [1 ]
机构
[1] TEXAS A&M UNIV SYST, DEPT VET PHYSIOL & PHARMACOL, COLL STN, TX 77843 USA
关键词
HALOGENATED AROMATICS; STRUCTURE-IMMUNOTOXICITY RELATIONSHIPS;
D O I
10.1016/0300-483X(93)90183-S
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The dose-dependent effects of a single acute exposure of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), 1,2,3,7,9-PeCDF, 1,3,6,8-tetrachlorodibenzofuran (TCDF), 3,3',4,4',5-pentachlorobiphenyl (pentaCB), and 3,3',4,4',5,5'-hexaCB on the suppression of the splenic plaque-forming cell (PFC) response to the T-cell-independent antigen trinitrophenyl-lipopolysaccharide were determined in C57BL/6 and DBA/2 mice. In addition, the induction of hepatic microsomal ethoxyresorufin O-deethylase (EROD) activity was also measured in these animals. 2,3,7,8-TCDD and 2,3,4,7,8-PeCDF were the most immunotoxic congeners in both strains of mice and with the exception of the latter congener, the ED50 values for each compound were lower in the C57BL/6 than the DBA/2 mice. 2,3,7,8-TCDD induced hepatic microsomal EROD activity in both strains of mice whereas the other congeners were considerably less active or inactive as inducers. The results of this study demonstrated that for the halogenated aromatic hydrocarbons the immunotoxic response was a more sensitive indicator of exposure than the induction of CYP1A1 activity. The rank order for the immunotoxic potencies of the chlorinated aromatic compounds used in this study was 2,3,7,8-TCDD - 2,3,4,7,8-PeCDF > 3,3',4,4',5-pentaCB almost-equal-to 3,3',4,4',5,5'-hexaCB > 1,2,3,7,9-PeCDF > 1,3,6,8-TCDF. The order of activity for these congeners was similar for other Ah receptor-mediated responses and these results coupled with the differential responsiveness of the C57BL/6 and DBA/2 mice confirms the role of aryl hydrocarbon (Ah) receptor in mediating the suppression of this T-cell-independent response.
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页码:217 / 227
页数:11
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