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多氯联苯和多溴联苯:对C57BL/6J和DBA/2J近交系小鼠的生物学和毒性作用

PCBs and PBBs: biologic and toxic effects on C57BL/6J and DBA/2J inbred mice.

作者信息

Robertson L W, Parkinson A, Bandiera S, Lambert I, Merrill J, Safe S H

出版信息

Toxicology. 1984 Jun;31(3-4):191-206. doi: 10.1016/0300-483x(84)90101-x.

Abstract

Treatment of genetically inbred "responsive" C57BL/6J and "non-responsive" DBA/2J mice with Aroclor 1254 or fireMaster BP-6 resulted in the induction of hepatic microsomal benzo[a]pyrene hydroxylase only in the former mouse strain and aminopyrine N-demethylase in both strains of mice. In contrast, 3,3',4,4',5-pentachlorobiphenyl and 3,3',4,4'-tetrabromobiphenyl, induced benzo[a]pyrene hydroxylase in both C57BL/6J and DBA/2J but did not enhance aminopyrine N-demethylase in either strain of mouse. Both these coplanar halogenated biphenyls also caused thymic atrophy in the responsive and non-responsive mice and their effects resembled those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Treatment of the inbred mice with several mono-ortho substituted analogs of the coplanar halogenated biphenyls, including 2,3,3',4,4'-pentachloro-, 2,3',4,4',5-pentabromo-, 2,3,3',4,4',5-hexachloro- and 3',4'-dibromo-2,3,4,5-tetrachlorobiphenyl, gave hepatic enzyme-induction results similar to those observed for the commercial halogenated biphenyls. At dose levels of 1500 mumol/kg, most of these compounds caused thymic atrophy in C57BL/6J mice but not in DBA/2J mice. The structure-activity correlations in the mice complement similar studies with the halogenated biphenyls in rats and support the proposed receptor-mediated mechanism for the toxic halogenated aromatics.

摘要

用多氯联苯混合物1254或防火剂BP - 6处理基因纯合的“反应性”C57BL/6J小鼠和“无反应性”DBA/2J小鼠,结果仅在前一种小鼠品系中诱导了肝微粒体苯并[a]芘羟化酶,而在两种小鼠品系中均诱导了氨基比林N - 脱甲基酶。相比之下,3,3',4,4',5 - 五氯联苯和3,3',4,4' - 四溴联苯在C57BL/6J和DBA/2J小鼠中均诱导了苯并[a]芘羟化酶,但在两种小鼠品系中均未增强氨基比林N - 脱甲基酶。这两种共平面卤代联苯还在反应性和无反应性小鼠中引起胸腺萎缩,其作用类似于2,3,7,8 - 四氯二苯并 - p - 二噁英(TCDD)。用几种共平面卤代联苯的单邻位取代类似物处理近交系小鼠,包括2,3,3',4,4' - 五氯 - 、2,3',4,4',5 - 五溴 - 、2,3,3',4,4',5 - 六氯 - 和3',4' - 二溴 - 2,3,4,5 - 四氯联苯,得到的肝酶诱导结果与商用卤代联苯观察到的结果相似。在剂量水平为1500 μmol/kg时,这些化合物中的大多数在C57BL/6J小鼠中引起胸腺萎缩,但在DBA/2J小鼠中未引起。小鼠中的构效关系补充了大鼠中卤代联苯的类似研究,并支持了所提出的有毒卤代芳烃受体介导机制。

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