Hornung Michael W, Cook Philip M, Fitzsimmons Patrick N, Kuehl Douglas W, Nichols John W
US Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Mid-Continent Ecology Division, Duluth, MN 55804, USA.
Toxicol Sci. 2007 Dec;100(2):393-405. doi: 10.1093/toxsci/kfm231. Epub 2007 Sep 5.
The need to understand chemical uptake, distribution, and metabolism in embryonic and larval fish derives from the fact that these early life stages often exhibit greater sensitivity to xenobiotic compounds than do adult animals. In this study, a 6-h acute waterborne exposure immediately after fertilization was used to quickly load the egg with benzo[a]pyrene (BaP). This exposure was used to mimic the initial egg concentration of a persistent bioaccumulative toxicant that could result from maternal transfer. We used multiphoton laser scanning microscopy (MPLSM) in combination with conventional analytical chemistry methods to characterize the tissue distribution of BaP and its principal metabolites in medaka embryos and post-hatch larvae. Embryonic metabolism of BaP was evident by MPLSM prior to liver formation or heart development. A major product of this metabolism was identified by liquid chromatography/mass spectrometry as BaP-3-glucuronide. MPLSM showed that metabolites were sequestered within the yolk, biliary system, and gastrointestinal tract. When the gastrointestinal tract became patent a few days after hatch, the metabolites were rapidly eliminated. These findings indicate that some of the earliest embryonic tissues are metabolically competent and that redistribution of BaP and its metabolic products occurs throughout development. Rapid metabolism of BaP substantially reduces the body burden of parent chemical in the developing embryo, potentially reducing toxicity. It remains unclear whether metabolism of BaP in medaka embryos leads to the formation of DNA adducts associated with genotoxic effects or yields metabolites that later lead to other toxicity in juveniles or adults.
了解胚胎期和幼鱼期鱼类对化学物质的摄取、分布和代谢情况很有必要，因为这些生命早期阶段通常比成年动物对外源化合物更为敏感。在本研究中，受精后立即进行6小时的急性水体暴露，以便使鱼卵快速摄取苯并[a]芘（BaP）。这种暴露用于模拟母体转移可能导致的持久性生物累积性毒物的初始鱼卵浓度。我们结合传统分析化学方法，使用多光子激光扫描显微镜（MPLSM）来表征BaP及其主要代谢产物在青鳉胚胎和孵化后幼鱼中的组织分布。在肝脏形成或心脏发育之前，MPLSM就已显示出BaP在胚胎中的代谢情况。通过液相色谱/质谱法鉴定出这种代谢的主要产物为BaP - 3 - 葡糖醛酸苷。MPLSM显示代谢产物被隔离在卵黄、胆道系统和胃肠道内。孵化几天后胃肠道贯通时，代谢产物迅速被清除。这些发现表明，一些最早的胚胎组织具有代谢能力，并且在整个发育过程中BaP及其代谢产物会重新分布。BaP的快速代谢显著降低了发育中胚胎体内母体化学物质的负担，可能降低毒性。目前尚不清楚青鳉胚胎中BaP的代谢是否会导致与遗传毒性效应相关的DNA加合物形成，或者产生的代谢产物是否会在幼鱼或成鱼后期导致其他毒性。
