Dickerson R, Howie L, Davis D, Safe S
Department of Veterinary Physiology & Pharmacology, Texas A&M University, College Station 77843.
Fundam Appl Toxicol. 1990 Aug;15(2):298-307. doi: 10.1016/0272-0590(90)90056-p.
The dose-response effects of the 1,2,3,4,6,7,8-, 1,2,3,4,7,8,9-, 1,2,3,4,6,8,9-, and 1,2,3,4,6,7,9-heptachlorodibenzofurans (HpCDFs) on the splenic plaque-forming cell (PFC) response to sheep erythrocytes and on the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin-O-deethylase (EROD) activities were determined in male C57BL/6 mice. The ED50 values for the decrease in the PFCs/spleen, the number of PFCs/10(6) viable cells, and the induction of AHH and EROD activities were 1,2,3,4,6,7,8-HpCDF, 0.011, 0.018, 0.11, and 0.315 mumol/kg, respectively; 1,2,3,4,7,8,9-HpCDF, 0.012, 0.054, 0.70, and 0.20 mumol/kg, respectively; 1,2,3,4,6,7,9-HpCDF, 1.2, 1.3, greater than 43, and greater than 43 mumol/kg, respectively; 1,2,3,4,6,8,9-HpCDF, 1.5, 3.4, 22, and 22 mumol/kg, respectively. It was apparent from these studies that the 2,3,7,8-substituted HpCDF isomers (1,2,3,4,6,7,8- and 1,2,3,4,7,8,9-) were significantly more potent than the compounds which contained only three lateral C1 groups. These results were obtained using a multiple dosing regimen in which 10 separate doses of the HpCDF isomers were administered to the mice by intraperitoneal injection over a period of 12 days. However, when the mice were treated with a single dose of an HpCDF congener, which was equivalent to the total dose used in the multiple dose study, the responses were comparable. A comparison of the relative immunotoxic potencies of the 2,3,7,8-substituted HpCDFs and 2,3,7,8-tetrachlorodibenzo-p-dioxin showed that the latter compound was approximately 10 times more active than the HpCDFs.
在雄性C57BL/6小鼠中，测定了1,2,3,4,6,7,8-、1,2,3,4,7,8,9-、1,2,3,4,6,8,9-和1,2,3,4,6,7,9-七氯二苯并呋喃（HpCDFs）对脾脏针对绵羊红细胞的斑块形成细胞（PFC）反应以及对肝微粒体芳烃羟化酶（AHH）和乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）活性诱导的剂量 - 反应效应。PFCs/脾脏减少、每10⁶个活细胞中PFCs数量以及AHH和EROD活性诱导的半数有效剂量（ED50）值分别为：1,2,3,4,6,7,8 - HpCDF，分别为0.011、0.018、0.11和0.315 μmol/kg；1,2,3,4,7,8,9 - HpCDF，分别为0.012、0.054、0.70和0.20 μmol/kg；1,2,3,4,6,7,9 - HpCDF，分别为1.2、1.3、大于43和大于43 μmol/kg；1,2,3,4,6,8,9 - HpCDF，分别为1.5、3.4、22和22 μmol/kg。从这些研究中可以明显看出，2,3,7,8 - 取代的HpCDF异构体（1,2,3,4,6,7,8 - 和1,2,3,4,7,8,9 - ）比仅含有三个侧链C1基团的化合物活性明显更强。这些结果是使用多剂量方案获得的，其中在12天内通过腹腔注射向小鼠给予10次单独剂量的HpCDF异构体。然而，当用相当于多剂量研究中使用的总剂量的单剂量HpCDF同系物处理小鼠时，反应相当。2,3,7,8 - 取代的HpCDFs与2,3,7,8 - 四氯二苯并 - p - 二恶英的相对免疫毒性效力比较表明，后一种化合物的活性比HpCDFs高约10倍。
