Shayer Rob, Kinchesh Paul, Raffray Mark, Kortenkamp Andreas
Department of Health Tobacco Policy Team Wellington House, 133-155 Waterloo Road SE1 8UG London, UK.
Biomarkers. 2004 Jan-Feb;9(1):32-46. doi: 10.1080/13547500310001659037.
The biomonitoring of individuals exposed to chromium(VI) by inhalation is often based on determinations of chromium in body fluids such as blood, plasma or urine, or on assessments of DNA damage in non-lung surrogate tissues such as peripheral blood lymphocytes. These techniques are of some use as biomarkers of internal exposure or biological effect, mainly in the case of soluble chromium(VI) compounds, but they provide at best only indirect information about chromium(VI) concentrations in the main target organ of interest - the lung. An urgent need exists for a non-invasive technique to permit the visualization and quantification of chromium(VI) in the lung of exposed humans. This study details the development of a lung imaging technique based on the detection of paramagnetic chromium using magnetic resonance imaging (MRI). The intracellular reductive conversion of chromium(VI) is a crucial bioactivation step in its carcinogenicity, and the MRI method described here relies on the conversion of non-paramagnetic (MRI 'silent') chromium(VI) to detectable paramagnetic species such as chromium(III). Initial studies with chromium(III) revealed that a range of 2.5-5 microg chromium(III) instilled in rat lung is considered to be the lower limit of detection of this method. It was possible to demonstrate the presence of 30 microg chromium(VI) in our post-mortem rat model. The ultimate objective of this work is to determine whether this technique has applicability to the biomonitoring of chromium(VI) inhalation exposures that result in internalized lung doses in human subjects.
对通过吸入接触六价铬的个体进行生物监测,通常基于对血液、血浆或尿液等体液中铬的测定,或对外周血淋巴细胞等非肺部替代组织中DNA损伤的评估。这些技术作为内暴露或生物效应的生物标志物有一定用途,主要适用于可溶性六价铬化合物的情况,但它们充其量只能提供有关主要目标器官——肺部中六价铬浓度的间接信息。迫切需要一种非侵入性技术,以便能够可视化并量化暴露人群肺部中的六价铬。本研究详细介绍了一种基于磁共振成像(MRI)检测顺磁性铬的肺部成像技术的开发过程。六价铬的细胞内还原转化是其致癌性中的关键生物活化步骤,此处描述的MRI方法依赖于将非顺磁性(MRI“无信号”)的六价铬转化为可检测的顺磁性物质,如三价铬。对三价铬的初步研究表明,向大鼠肺部注入2.5至5微克三价铬的范围被认为是该方法的检测下限。在我们的大鼠死后模型中能够证明存在30微克六价铬。这项工作的最终目标是确定该技术是否适用于对导致人体受试者肺部摄入剂量的六价铬吸入暴露进行生物监测。