Philips Blythe H, Susman Thomas C, Powell Wade H
Biology Department, Kenyon College, Gambier, OH, USA.
Mar Environ Res. 2006 Jul;62 Suppl:S34-7. doi: 10.1016/j.marenvres.2006.04.027. Epub 2006 Apr 18.
Although 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a potent developmental toxicant in most vertebrates, several frog species are insensitive to TCDD, especially during early life stages. Previous experiments with ranid frogs suggest that TCDD insensitivity results largely from rapid elimination. Recent studies in the African clawed frog (Xenopus laevis; family Pipidae) link low TCDD toxicity with the low binding affinity of aryl hydrocarbon receptors, which mediate the toxic effects of dioxin-like compounds. The present study sought to examine TCDD elimination in X. laevis embryos and tadpoles, enabling an integrated assessment of the relative roles of TCDD elimination and AHR-related mechanisms in TCDD insensitivity within a single frog species. Using tadpoles (stage 52-55; approximately 1 month old) exposed to [3H]TCDD, we observed that TCDD has a relatively short half life of 102.6 h, consistent with other frogs and much faster than reported clearance rates in developing fish. In contrast, TCDD elimination is much slower during early development. Embryos exposed during primary organogenesis (from stage 31-41, beginning approximately 36 h after fertilization) exhibited little TCDD elimination during the subsequent 96 h. Enhanced TCDD clearance in later developmental stages may follow the appearance of a functional digestive tract and the onset of feeding. These results suggest that rapid elimination is unlikely to contribute mechanistically to TCDD insensitivity during development of the cardiovascular system, which is significantly perturbed by TCDD in fish embryos.
尽管2,3,7,8-四氯二苯并对二恶英（TCDD）对大多数脊椎动物来说是一种强效发育毒物，但几种蛙类对TCDD不敏感，尤其是在生命早期阶段。之前对蛙科蛙类的实验表明，TCDD不敏感性很大程度上源于快速消除。最近对非洲爪蟾（非洲爪蟾；负子蟾科）的研究将低TCDD毒性与芳烃受体的低结合亲和力联系起来，芳烃受体介导二恶英类化合物的毒性作用。本研究旨在检测非洲爪蟾胚胎和蝌蚪中TCDD的消除情况，以便在单一蛙类物种中综合评估TCDD消除和AHR相关机制在TCDD不敏感性中的相对作用。使用暴露于[3H]TCDD的蝌蚪（52-55期；约1月龄），我们观察到TCDD的半衰期相对较短，为102.6小时，这与其他蛙类一致，且比发育中的鱼类报道的清除率快得多。相比之下，TCDD在早期发育过程中的消除要慢得多。在主要器官发生期（31-41期，受精后约36小时开始）暴露的胚胎在随后的96小时内几乎没有TCDD消除。后期发育阶段TCDD清除率的提高可能与功能性消化道的出现和摄食的开始有关。这些结果表明，在心血管系统发育过程中，快速消除在机制上不太可能导致对TCDD的不敏感性，而心血管系统在鱼类胚胎中会受到TCDD的显著干扰。
