Sholts Sabrina B, Esteban Javier, Herlin Maria, Viluksela Matti, Håkansson Helen
Department of Anthropology, National Museum of Natural History, Smithsonian Institution, 10th and Constitution Avenue NW, Washington, DC 20560, USA.
Instituto de Bioingeniería, Universidad Miguel Hernández, Av. de la Universidad s/n, 03202 Elche (Alicante), Spain.
Toxicol Rep. 2014 Dec 19;2:472-481. doi: 10.1016/j.toxrep.2014.12.007. eCollection 2015.
Mammalian bone has shown a variety of responses to 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) exposure in experimental and wildlife studies. Although many responses have been well characterized in the postcranial skeleton, dioxin-induced effects on the cranium are largely unknown. In this study, we investigated the effects of chronic adult exposure to TCDD on cranial size and shape in dioxin-resistant Han/Wistar (H/W) and dioxin-sensitive Long-Evans (L-E) rat strains. Three-dimensional landmark configurations for the face, vault, and base of the cranium were recorded and analyzed using geometric morphometrics (GM) and dose-response modeling. The strongest effects were shown by L-E and H/W rats with daily exposures of 100 and 1000 ng TCDD/kg bw/day, respectively, resulting in significant reductions in centroid size (CS) in all three cranial modules for both strains except for the vault in H/W rats. Consistent with previous evidence of intraspecific variation in TCDD resistance, the benchmark doses (CEDs) for cranial size reduction in L-E rats were roughly 10-fold lower than those for H/W rats. For both strains, the face showed the greatest size reduction from the highest doses of TCDD (i.e., 3.6 and 6.3% decreases in H/W and L-E rats, respectively), most likely related to dose-dependent reductions in limb bone size and body weight gain. However, intrinsic morphological differences between strains were also observed: although the control groups of H/W and L-E rats had vaults and bases of comparable size, the face was 6.4% larger in L-E rats. Thus, although H/W rats possess an altered aryl hydrocarbon receptor (AhR) that appears to mediate and provides some resistance to TCDD exposure, their smaller reductions in facial size may also relate to strain-specific patterns of cranial development and growth. Future research will be aimed at understanding how ontogenetic factors may modulate toxic effects of prenatal and lactational exposure on the mammalian skeleton.
在实验研究和野生动物研究中，哺乳动物骨骼对2,3,7,8 - 四氯二苯并 - 对二恶英（TCDD）暴露呈现出多种反应。尽管许多反应在后颅骨骼中已有充分描述，但二恶英对颅骨的影响在很大程度上仍不清楚。在本研究中，我们调查了成年大鼠长期暴露于TCDD对二恶英抗性的Han/Wistar（H/W）和二恶英敏感的Long - Evans（L - E）大鼠品系颅骨大小和形状的影响。使用几何形态计量学（GM）和剂量反应模型记录并分析了颅骨面部、颅顶和颅底的三维地标构型。L - E和H/W大鼠分别每日暴露于100和1000 ng TCDD/kg体重/天，表现出最强的效应，导致两个品系所有三个颅骨模块的质心大小（CS）显著减小，但H/W大鼠的颅顶除外。与先前关于TCDD抗性种内变异的证据一致，L - E大鼠颅骨大小减小的基准剂量（CEDs）比H/W大鼠低约10倍。对于两个品系，面部在最高剂量的TCDD作用下减小幅度最大（即H/W和L - E大鼠分别减少3.6%和6.3%），这很可能与四肢骨大小和体重增加的剂量依赖性减少有关。然而，也观察到品系之间的内在形态差异：尽管H/W和L - E大鼠的对照组颅顶和颅底大小相当，但L - E大鼠的面部大6.4%。因此，尽管H/W大鼠具有改变的芳烃受体（AhR），似乎能介导并对TCDD暴露提供一定抗性，但其面部较小的减小幅度也可能与颅骨发育和生长的品系特异性模式有关。未来的研究将致力于理解个体发育因素如何调节产前和哺乳期暴露对哺乳动物骨骼的毒性作用。
