Ahmed A E, Ansari G A, Dencker L, Ullberg S
Department of Pathology, University of Texas Medical Branch, Galveston 77550.
Fundam Appl Toxicol. 1991 Feb;16(2):356-64.
The placental transport and localization in fetal and maternal tissues of 14C-BHA isomers, 2-t-[methyl-14C]butyl-4-hydroxyanisole (2-BHA) and 3-t-[methyl-14C]butyl-4-hydroxyanisole (3-BHA), were studied in pregnant mice by whole-body autoradiography techniques. BHA isomers were given (iv 50 microCi/100 g as a tracer dose) to pregnant mice at Day 11 (organogenesis) and Day 18 (postorganogenesis) of gestation. Peak levels of radioactivity occurred in various tissues 1-4 hr after iv administration of both isomers. 3-BHA and its metabolites have a higher affinity to fatty tissues and livers of pregnant mice. The concentration of radiocarbon in maternal liver and brown fat following treatment with 14C-3-BHA was much higher than the radioactivity concentration in the corresponding tissues of mothers treated with 2-BHA. On the other hand, the fetal concentration of radioactivity was higher in animals treated with 2-BHA than in those treated with 3-BHA. The radioactivity derived from both isomers accumulated in the fetal gastrointestinal tract. In both groups the radioactivity accumulated in the maternal nasal cavity and mucosa and the gastrointestinal contents. At 24 hr after treatment, retention of radioactivity in maternal lungs, amniotic fluid, and fetal gastrointestinal tissues was observed. Results from this study indicate that there are differences in the magnitude and extent of placental transport of 3-BHA and 2-BHA. Differences also exist in maternal organ uptake and radioactivity distribution of both isomers. Findings from this study are consistent with pharmacological differences existing between the isomers.
采用全身放射自显影技术,在妊娠小鼠中研究了14C - BHA异构体(2 - t - [甲基 - 14C]丁基 - 4 - 羟基茴香醚(2 - BHA)和3 - t - [甲基 - 14C]丁基 - 4 - 羟基茴香醚(3 - BHA))在胎盘的转运以及在胎儿和母体组织中的定位。在妊娠第11天(器官形成期)和第18天(器官形成后期),给妊娠小鼠静脉注射BHA异构体(作为示踪剂量,50微居里/100克)。静脉注射两种异构体后1 - 4小时,各组织中放射性达到峰值水平。3 - BHA及其代谢产物对妊娠小鼠的脂肪组织和肝脏具有更高的亲和力。用14C - 3 - BHA处理后,母体肝脏和棕色脂肪中的放射性碳浓度远高于用2 - BHA处理的母体相应组织中的放射性浓度。另一方面,用2 - BHA处理的动物胎儿中的放射性浓度高于用3 - BHA处理的动物。两种异构体产生的放射性都在胎儿胃肠道中蓄积。两组中,放射性均在母体鼻腔、黏膜和胃肠道内容物中蓄积。处理后24小时,观察到放射性在母体肺、羊水和胎儿胃肠道组织中的滞留。本研究结果表明,3 - BHA和2 - BHA在胎盘转运的程度和范围上存在差异。两种异构体在母体器官摄取和放射性分布方面也存在差异。本研究结果与异构体之间存在的药理学差异一致。