Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, IA, 52242, USA.
Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, 52242, USA.
Environ Pollut. 2020 Nov;266(Pt 1):115233. doi: 10.1016/j.envpol.2020.115233. Epub 2020 Jul 18.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants that are linked to adverse health outcomes. PCB tissue levels are determinants of PCB toxicity; however, it is unclear how factors, such as an altered metabolism and/or a fatty liver, affect PCB distribution in vivo. We determined the congener-specific disposition of PCBs in mice with a liver-specific deletion of cytochrome P450 reductase (KO), a model of fatty liver with impaired hepatic metabolism, and wild-type (WT) mice. Eight-week-old male WT (M, n = 3), male KO (M, n = 5), female WT (F, n = 4), and female KO mice (F, n = 4) were exposed orally to Aroclor 1254. PCBs were quantified in adipose, blood, brain, and liver tissues by gas chromatography-mass spectrometry. The ΣPCB levels followed the rank order adipose > liver ∼ brain > blood in WT and adipose ∼ liver > brain > blood in KO mice. PCB levels were much higher in the liver of KO than WT mice, irrespective of the sex. A comparison across exposure groups revealed minor genotype and sex-dependent differences in the PCB congener profiles (cos Θ > 0.92). Within each exposure group, tissue profiles showed small differences between tissues (cos Θ = 0.85 to 0.98). These differences were due to a decrease in metabolically more labile PCB congeners and an increase in congeners resistant to metabolism. The tissue-to-blood ratio of PCBs decreased for adipose, increased for the brain, and remained constant for the liver with an increase in chlorination. While these ratios did not follow the trends predicted using a composition-based model, the agreement between experimental and calculated partition coefficients was reasonable. Although the distribution of PCBs differs between KO and WT mice, the magnitude of the partitioning of PCBs from the blood into tissues can be approximated using composition-based models.
多氯联苯（PCBs）是持久性有机污染物，与不良健康结果有关。PCBs 组织水平是 PCB 毒性的决定因素；然而，目前尚不清楚代谢改变和/或脂肪肝等因素如何影响体内 PCB 的分布。我们确定了具有肝特异性细胞色素 P450 还原酶（KO）缺失的小鼠（脂肪肝模型，其肝代谢受损）和野生型（WT）小鼠中 PCB 同种型特异性的处置。将 8 周龄雄性 WT（M，n=3）、雄性 KO（M，n=5）、雌性 WT（F，n=4）和雌性 KO 小鼠（F，n=4）经口暴露于 Aroclor 1254。通过气相色谱-质谱法定量检测脂肪、血液、大脑和肝脏组织中的 PCBs。ΣPCB 水平在 WT 小鼠中按脂肪组织＞肝脏～大脑＞血液的顺序排列，在 KO 小鼠中按脂肪组织～肝脏＞大脑＞血液的顺序排列。KO 小鼠的肝脏中 PCB 水平远高于 WT 小鼠，与性别无关。不同暴露组之间的比较表明，PCBs 同系物图谱存在较小的基因型和性别依赖性差异（cosθ＞0.92）。在每个暴露组内，组织图谱显示组织之间的差异较小（cosθ=0.85 至 0.98）。这些差异是由于代谢更不稳定的 PCB 同系物减少和对代谢有抗性的同系物增加所致。随着氯化程度的增加，PCBs 的组织-血液比值对脂肪组织降低，对大脑组织增加，对肝脏组织保持不变。虽然这些比值不符合基于组成的模型预测的趋势，但实验和计算分配系数之间的一致性是合理的。尽管 KO 和 WT 小鼠之间的 PCB 分布不同，但可以使用基于组成的模型近似估计 PCBs 从血液分配到组织的程度。
