Montenegro Marcelo Freitas, Barbosa Fernando, Tanus-Santos Jose E
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of São Paulo, Ribeirao Preto, SP, Brazil.
Basic Clin Pharmacol Toxicol. 2008 Apr;102(4):347-51. doi: 10.1111/j.1742-7843.2007.00205.x. Epub 2008 Feb 12.
Pregnant women are one of the most sensitive populations to the toxic effects associated with lead (Pb) exposure. These effects are primarily associated with plasma Pb (Pb-P), which reflects the most rapidly exchangeable fraction of Pb in the bloodstream, and elevated maternal Pb-P may be more relevant to foetal Pb exposure than whole blood Pb (Pb-B). We investigated how pregnancy affects Pb-B, Pb-P and %Pb-P/Pb-B ratios without the influence of the delta-aminolevulinic acid dehydratase (ALAD) G177C polymorphism, which is a major genetic factor influencing Pb-B, Pb-P and %Pb-P/Pb-B ratios. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion in nine pregnant and 20 non-pregnant women, aged 18-33, environmentally exposed to Pb. Here, we included only women with ALAD 1-1 genotype. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. We found no differences in Pb-B (P > 0.05). However, pregnant women had a 2-fold increase in Pb-P and a 3-fold increase in %Pb-P/Pb-B (both P < 0.01) compared to non-pregnant women. These alterations in Pb concentrations associated with pregnancy are similar to those associated with different ALAD gene variants. We can now better appreciate how pregnancy affects foetal exposure to Pb without the influence of this important genetic factor.
孕妇是对铅(Pb)暴露相关毒性作用最敏感的人群之一。这些影响主要与血浆铅(Pb-P)有关,血浆铅反映了血液中铅最易快速交换的部分,与全血铅(Pb-B)相比,孕妇血浆铅升高可能与胎儿铅暴露更相关。我们研究了妊娠如何影响Pb-B、Pb-P和%Pb-P/Pb-B比值,而不受δ-氨基乙酰丙酸脱水酶(ALAD)G177C多态性的影响,该多态性是影响Pb-B、Pb-P和%Pb-P/Pb-B比值的主要遗传因素。通过PCR和限制性片段长度消化法,对18-33岁、环境暴露于铅的9名孕妇和20名非孕妇的ALAD G177C多态性基因型进行了测定。在这里,我们仅纳入了ALAD 1-1基因型的女性。分别通过电感耦合等离子体质谱法和石墨炉原子吸收光谱法测定Pb-P和Pb-B。我们发现Pb-B没有差异(P>0.05)。然而,与非孕妇相比,孕妇的Pb-P增加了2倍,%Pb-P/Pb-B增加了3倍(两者P<0.01)。与妊娠相关的铅浓度变化与不同ALAD基因变体相关的变化相似。现在我们可以更好地理解妊娠如何在没有这个重要遗传因素影响的情况下影响胎儿对铅的暴露。