Jönsson C J, Lund B O, Bergman A, Brandt I
Department of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala.
Reprod Toxicol. 1992;6(3):233-40. doi: 10.1016/0890-6238(92)90178-v.
Irreversible binding and toxicity of the DDT metabolite 3-methylsulphonyl-DDE (MeSO2-DDE) were examined in fetuses and suckling pups following administration to pregnant or lactating C57Bl mice. Tape-section autoradiography showed a high and tissue-specific accumulation and binding of MeSO2-DDE-14C-derived radioactivity in the late gestational fetal adrenal cortex. According to microautoradiography an irreversibly bound residue was confined to the zona fasciculata. Similarly, there was a high concentration of irreversibly bound 14C-labelled material in the adrenal zona fasciculata of suckling pups. Intraperitoneal injection of MeSO2-DDE-14C to lactating mice resulted in higher concentrations of radioactivity in the liver and stomach contents (milk) of the suckling pups than in the maternal liver. This treatment also resulted in a higher level of radioactivity in the adrenals of the pups than in the maternal adrenals, both at a subtoxic and at a toxic dose. Histopathologic examination of adrenals from suckling pups revealed extensive vacuolation and necrosis of the zona fasciculata 2 days following a single dose of MeSO2-DDE (25 mg/kg) to the dam. In the fetal adrenal zona fasciculata, slight degenerative changes were observed following a maternal dose of 50 mg/kg. In conclusion, the study shows that MeSO2-DDE is a highly tissue-specific toxicant to the fetal and postnatal adrenal zona fasciculata in mice. Based on the present data and on previous results in adult mice, we propose that a tissue-specific activation to a reactive metabolite in the fetal and postnatal adrenal cortex is mediated by cytochrome P-450 (11 beta).
在给怀孕或哺乳期的C57Bl小鼠施用滴滴涕代谢物3-甲基磺酰基-滴滴伊（MeSO2-DDE）后，研究了其对胎儿和乳鼠的不可逆结合及毒性。胶带切片放射自显影显示，在妊娠晚期胎儿肾上腺皮质中，MeSO2-DDE-14C衍生的放射性有高度且组织特异性的积累和结合。根据显微放射自显影，不可逆结合的残留物局限于束状带。同样，在乳鼠的肾上腺束状带中也有高浓度的不可逆结合的14C标记物质。给哺乳期小鼠腹腔注射MeSO2-DDE-14C，导致乳鼠肝脏和胃内容物（乳汁）中的放射性浓度高于母鼠肝脏。这种处理还导致在亚毒性和毒性剂量下，幼崽肾上腺中的放射性水平高于母鼠肾上腺。对乳鼠肾上腺进行组织病理学检查发现，在给母鼠单次注射MeSO2-DDE（25mg/kg）后2天，束状带出现广泛空泡化和坏死。在胎儿肾上腺束状带中，母体剂量为50mg/kg后观察到轻微的退行性变化。总之，该研究表明MeSO2-DDE是一种对小鼠胎儿和出生后肾上腺束状带具有高度组织特异性的毒物。基于目前的数据和之前对成年小鼠的研究结果，我们提出，胎儿和出生后肾上腺皮质中对活性代谢物的组织特异性激活是由细胞色素P-450（11β）介导的。
