Brouwer A, Blaner W S, Kukler A, Van den Berg K J
Radiobiological Institute TNO, Rijswijk, The Netherlands.
Chem Biol Interact. 1988;68(3-4):203-17. doi: 10.1016/0009-2797(88)90017-8.
The mechanism of plasma retinol reduction in rodents by 3,4,3',4'-tetrachlorobiphenyl (TCB) was investigated by radioimmunochemical analysis of the amounts of circulating and hepatic retinol-binding protein (RBP) and transthyretin (TTR) in exposed and control animals. Plasma RBP concentrations were markedly reduced in C57BL/Rij mice (50%) at 4 days, in DBA/2 mice (37-41%) at 4 and 8 days, and in Sprague-Dawley rats (58%) at 2 days after exposure to TCB. These reductions paralleled the time course of reduction of plasma retinol after exposure to TCB. Hepatic RBP concentrations were somewhat increased in TCB-treated animals, especially in the C57BL/Rij mouse and Sprague-Dawley rat. However, the release of hepatic RBP into the circulation was not blocked by TCB treatment, as analysed in vitamin A deficient rats. In addition, the amount of plasma TTR was in the normal range in TCB-treated rats. The dissociation constants of the RBP-TTR complex as analysed by polarization of fluorescence appeared to be significantly increased (from 0.5 x 10(-7) M-1 to 2.4 x 10(-7) M-1) in the presence of a TCB metabolite, isolated from plasma of TCB-treated rats. In addition, the estimated number of binding sites for RBP on the TTR molecule was reduced (from 2.8 to 1.7 sites) upon treatment of TTR with the TCB metabolite. These data support the hypothesis that plasma retinol reduction by TCB might result from a weakening of the RBP-TTR complex, in the presence of the TCB metabolite bound to the TTR.
通过对暴露组和对照组动物循环及肝脏视黄醇结合蛋白（RBP）和转甲状腺素蛋白（TTR）含量进行放射免疫化学分析，研究了3,4,3',4'-四氯联苯（TCB）降低啮齿动物血浆视黄醇的机制。暴露于TCB后4天，C57BL/Rij小鼠血浆RBP浓度显著降低（50%）；4天和8天时，DBA/2小鼠血浆RBP浓度降低（37 - 41%）；2天时，Sprague-Dawley大鼠血浆RBP浓度降低（58%）。这些降低与暴露于TCB后血浆视黄醇降低的时间进程平行。在经TCB处理的动物中，肝脏RBP浓度有所增加，尤其是在C57BL/Rij小鼠和Sprague-Dawley大鼠中。然而，正如在维生素A缺乏大鼠中所分析的那样，经TCB处理并未阻止肝脏RBP释放到循环中。此外，经TCB处理的大鼠血浆TTR含量在正常范围内。从经TCB处理的大鼠血浆中分离出的一种TCB代谢产物存在时，通过荧光偏振分析的RBP-TTR复合物解离常数似乎显著增加（从0.5×10⁻⁷ M⁻¹增加到2.4×10⁻⁷ M⁻¹）。此外，用TCB代谢产物处理TTR后，TTR分子上RBP的结合位点估计数量减少（从2.8个位点减少到1.7个位点）。这些数据支持这样一种假说，即TCB导致血浆视黄醇降低可能是由于在与TTR结合的TCB代谢产物存在的情况下，RBP-TTR复合物减弱所致。
