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Partitioning of benzene in blood: influence of hemoglobin type in humans and animals.

机译:血液中苯的分配:对人类和动物血红蛋白类型的影响。

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摘要

Earlier studies have shown that air/blood partition coefficients (PCs) for many volatile organic chemicals (VOCs) are much higher in rat blood than in human blood. It has been suggested that the discrepancy could be attributed to the fact that hemoglobin (Hb) in rat blood exists in a quasi-crystalline form of hydrophobicity greater than that of normal human Hb (HbA) and thus has a higher carrying capacity for VOCs. In the present study, we used benzene as a prototypic VOC to examine its relative partitioning into human and animal blood. Additionally, we sought to ascertain whether the water-insoluble form of hemoglobin (HbS) found in subjects with homozygous sickle cell (SC) disease has a greater VOC-carrying capacity than does HbA blood. At a low-O(2) tension, HbS switches to water-insoluble polymers, which physically deforms the red blood cells (RBCs) to the sickle shape. We equilibrated HbA, HbS, Hartley guinea pig, CD1 mouse, and rat (F-344, Wistar, and Sprague-Dawley) blood and their respective fractions with benzene vapor (80 or 400 ppm) for 3 hr at 37 degrees C in air-tight vials. We introduced benzene vapor into the vial head space that contained air or respiratory mixtures of venous-type (low-O(2)) or arterial-type (high-O(2)) gases. The blood measurements included the PC, Hb, partial pressures of O(2)(pO(2)) and CO(2)(pCO(2), pH, and percentage of SCs. The benzene concentration had no effect on these parameters, and the high- and low-O(2) gas mixtures produced the expected changes in pO(2), pCO(2), and pH. At equilibrium, the low-O(2) HbS blood had approximately 85% SCs compared with roughly 15% with air or high-O(2) gas. PCs for rat and mouse blood were about 100% higher than those for human and guinea pig blood, but the PC for deoxygenated HbS blood was only slightly higher than that for HbA or oxygenated HbS blood. Benzene showed higher affinities for RBCs in the deoxygenated HbS, rat, and mouse blood and higher affinity for plasma in the guinea pig blood. There was no evidence of disproportionate partitioning of benzene into oxygenated HbS or into HbA blood forms. These data suggest that the water solubility of Hb alone appears to have little effect on the VOC-carrying capacity of blood and that the influence of species is large in comparison. These latter differences in partitioning may depend on the number of hydrophobic sites on the surface of the plasma/heme proteins and thus be unique to the species.
机译:早期的研究表明,大鼠血液中许多挥发性有机化学物质(VOC)的空气/血液分配系数(PCs)远高于人类血液。有人认为,这种差异可归因于以下事实:大鼠血液中的血红蛋白(Hb)以比正常人Hb(HbA)大的疏水性的准结晶形式存在,因此对VOC的携带能力更高。在本研究中,我们使用苯作为原型VOC来检查其在人和动物血液中的相对分配。此外,我们试图确定在患有纯合镰状细胞(SC)疾病的受试者中发现的非水溶性形式的血红蛋白(HbS)是否具有比HbA血液更大的VOC携带能力。在低O(2)张力下,HbS切换为不溶于水的聚合物,该聚合物将红细胞(RBC)物理变形为镰刀状。我们在37摄氏度的空气中将HbA,HbS,Hartley豚鼠,CD1小鼠和大鼠(F-344,Wistar和Sprague-Dawley)血液及其各自的馏分与苯蒸气(80或400 ppm)平衡了3小时-密封小瓶。我们将苯蒸气引入到小瓶顶部空间,其中包含空气或静脉型(低O(2))或动脉型(高O(2))气体的呼吸混合物。血液测量包括PC,Hb,O(2)(pO(2))和CO(2)(pCO(2))的分压,pH值和SC的百分比。苯浓度对这些参数没有影响,高和低O(2)气体混合物产生了pO(2),pCO(2)和pH值的预期变化;在平衡状态下,低O(2)HbS血液的SC约为85%大约15%的空气或高O(2)气体大鼠和小鼠血液中的PC比人和豚鼠血液中的PC高约100%,而脱氧HbS血液中的PC仅比HbA或PC中的PC略高苯在脱氧HbS,大鼠和小鼠血液中对RBC具有更高的亲和力,在豚鼠血液中对血浆具有更高的亲和力,没有证据表明苯不成比例地分配到氧化HbS或HbA血型中。数据表明,单独的Hb水溶性似乎对血液中VOC的承载能力影响很小,相比较而言,物种数量很大。后面这些分配上的差异可能取决于血浆/血红素蛋白表面疏水位点的数量,因此对于物种而言是唯一的。

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